Electrophysiological signatures of atypical intrinsic brain connectivity networks in autism

NASA Astrophysics Data System (ADS)

Shou, Guofa; Mosconi, Matthew W.; Wang, Jun; Ethridge, Lauren E.; Sweeney, John A.; Ding, Lei

2017-08-01

Objective. Abnormal local and long-range brain connectivity have been widely reported in autism spectrum disorder (ASD), yet the nature of these abnormalities and their functional relevance at distinct cortical rhythms remains unknown. Investigations of intrinsic connectivity networks (ICNs) and their coherence across whole brain networks hold promise for determining whether patterns of functional connectivity abnormalities vary across frequencies and networks in ASD. In the present study, we aimed to probe atypical intrinsic brain connectivity networks in ASD from resting-state electroencephalography (EEG) data via characterizing the whole brain network. Approach. Connectivity within individual ICNs (measured by spectral power) and between ICNs (measured by coherence) were examined at four canonical frequency bands via a time-frequency independent component analysis on high-density EEG, which were recorded from 20 ASD and 20 typical developing (TD) subjects during an eyes-closed resting state. Main results. Among twelve identified electrophysiological ICNs, individuals with ASD showed hyper-connectivity in individual ICNs and hypo-connectivity between ICNs. Functional connectivity alterations in ASD were more severe in the frontal lobe and the default mode network (DMN) and at low frequency bands. These functional connectivity measures also showed abnormal age-related associations in ICNs related to frontal, temporal and motor regions in ASD. Significance. Our findings suggest that ASD is characterized by the opposite directions of abnormalities (i.e. hypo- and hyper-connectivity) in the hierarchical structure of the whole brain network, with more impairments in the frontal lobe and the DMN at low frequency bands, which are critical for top-down control of sensory systems, as well as for both cognition and social skills.

Technetium-99m-HMPAO SPECT in the evaluation of patients with a remote history of traumatic brain injury: a comparison with x-ray computed tomography.

PubMed

Gray, B G; Ichise, M; Chung, D G; Kirsh, J C; Franks, W

1992-01-01

The functional imaging modality has potential for demonstrating parenchymal abnormalities not detectable by traditional morphological imaging. Fifty-three patients with a remote history of traumatic brain injury (TBI) were studied with SPECT using 99mTc-hexamethylpropyleneamineoxime (HMPAO) and x-ray computed tomography (CT). Overall, 42 patients (80%) showed regional cerebral blood flow (rCBF) deficits by HMPAO SPECT, whereas 29 patients (55%) showed morphological abnormalities by CT. Out of 20 patients with minor head injury, 12 patients (60%) showed rCBF deficits and 5 patients (25%) showed CT abnormalities. Of 33 patients with major head injury, 30 patients (90%) showed rCBF deficits and 24 patients (72%) showed CT abnormalities. Thus, HMPAO SPECT was more sensitive than CT in detecting abnormalities in patients with a history of TBI, particularly in the minor head injury group. In the major head injury group, three patients showed localized cortical atrophy by CT and normal rCBF by HMPAO SPECT. In the evaluation of TBI patients, HMPAO SPECT is a useful technique to demonstrate regional brain dysfunction in the presence of morphological integrity as assessed by CT.

Left globus pallidus abnormality in never-medicated patients with schizophrenia

DOE Office of Scientific and Technical Information (OSTI.GOV)

Early, T.S.; Reiman, E.M.; Raichle, M.E.

1987-01-01

Schizophrenia is a severe psychiatric disorder characterized by onset in young adulthood, the occurrence of hallucinations and delusions, and the development of enduring psychosocial disability. The pathophysiology of this disorder remains unknown. Studies of cerebral blood flow and metabolism designed to identify brain abnormalities in schizophrenia have been limited by inadequate methods of anatomical localization and the possibility of persistent medication effects. The authors have now used positron emission tomography and a validated method of anatomical localization in an attempt to identify abnormalities of regional cerebral blood flow in newly diagnosed never-medicated patients with schizophrenia. An exploratory study of 5more » patients and 10 normal control subjects identified abnormally high blood flow in the left globus pallidus of patients with schizophrenia. A replication study of 5 additional patients and 10 additional control subjects confirmed this finding. No other abnormalities were found.« less

Abnormal regional homogeneity as a potential imaging biomarker for adolescent-onset schizophrenia: A resting-state fMRI study and support vector machine analysis.

PubMed

Wang, Shuai; Zhang, Yan; Lv, Luxian; Wu, Renrong; Fan, Xiaoduo; Zhao, Jingping; Guo, Wenbin

2018-02-01

Structural and functional abnormalities have been reported in the brain of patients with adolescent-onset schizophrenia (AOS). The brain regional functional synchronization in patients with AOS remains unclear. We analyzed resting-state functional magnetic resonance scans in 48 drug-naive patients with AOS and 31 healthy controls by using regional homogeneity (ReHo), a measurement that reflects brain local functional connectivity or synchronization and indicates regional integration of information processing. Then, receiver operating characteristic curves and support vector machines were used to evaluate the effect of abnormal regional homogeneity in differentiating patients from controls. Patients with AOS showed significantly increased ReHo values in the bilateral superior medial prefrontal cortex (MPFC) and significantly decreased ReHo values in the left superior temporal gyrus (STG), right precentral lobule, right inferior parietal lobule (IPL), and left paracentral lobule when compared with controls. A combination of the ReHo values in bilateral superior MPFC, left STG, and right IPL was able to discriminate patients from controls with the sensitivity of 88.24%, specificity of 91.89%, and accuracy of 90.14%. The brain regional functional synchronization abnormalities exist in drug-naive patients with AOS. A combination of ReHo values in these abnormal regions might serve as potential imaging biomarker to identify patients with AOS. Copyright © 2017 Elsevier B.V. All rights reserved.

Coupled brain and urine spectroscopy - in vivo metabolomic characterization of HMG-CoA lyase deficiency in 5 patients.

PubMed

Roland, Dominique; Jissendi-Tchofo, Patrice; Briand, Gilbert; Vamecq, Joseph; Fontaine, Monique; Ultré, Vincent; Acquaviva-Bourdain, Cécile; Mention, Karine; Dobbelaere, Dries

2017-06-01

3-Hydroxy-3-Methylglutaryl-Coenzyme A (HMG-CoA) lyase deficiency is a rare inborn error of leucine metabolism and ketogenesis. Despite recurrent hypoglycemia and metabolic decompensations, most patients have a good clinical and neurological outcome contrasting with abnormal brain magnetic resonance imaging (MRI) signals and consistent abnormal brain proton magnetic resonance spectroscopy ( 1 H-MRS) metabolite peaks. Identifying these metabolites could provide surrogate markers of the disease and improve understanding of MRI-clinical discrepancy and follow-up of affected patients. Urine samples, brain MRI and 1 H-MRS in 5 patients with HMG-CoA lyase deficiency (4 boys and 1 girl aged from 25days to 10years) were, for each patient, obtained on the same day. Brain and urine spectroscopy were performed at the same pH by studying urine at pH 7.4. Due to pH-induced modifications in chemical shifts and because reference 1 H NMR spectra are obtained at pH 2.5, spectroscopy of normal urine added with the suspected metabolite was further performed at this pH to validate the correct identification of compounds. Mild to extended abnormal white matter MRI signals were observed in all cases. Brain spectroscopy abnormal peaks at 0.8-1.1ppm, 1.2-1.4ppm and 2.4ppm were also detected by urine spectroscopy at pH 7.4. Taking into account pH-induced changes in chemical shifts, brain abnormal peaks in patients were formally identified to be those of 3-hydroxyisovaleric, 3-methylglutaconic, 3-methylglutaric and 3-hydroxy-3-methylglutaric acids. 3-Methylglutaric, 3-hydroxyisovaleric and 3-hydroxy-3-methylglutaric acids identified on urine 1 H-NMR spectra of 5 patients with HMG-CoA lyase deficiency are responsible for the cerebral spectroscopy signature seen in these patients, validating their local involvement in brain and putative contribution to brain neuropathology. Copyright © 2017 Elsevier Inc. All rights reserved.

Altered brain structural networks in attention deficit/hyperactivity disorder children revealed by cortical thickness.

PubMed

Liu, Tian; Chen, Yanni; Li, Chenxi; Li, Youjun; Wang, Jue

2017-07-04

This study investigated the cortical thickness and topological features of human brain anatomical networks related to attention deficit/hyperactivity disorder. Data were collected from 40 attention deficit/hyperactivity disorder children and 40 normal control children. Interregional correlation matrices were established by calculating the correlations of cortical thickness between all pairs of cortical regions (68 regions) of the whole brain. Further thresholds were applied to create binary matrices to construct a series of undirected and unweighted graphs, and global, local, and nodal efficiencies were computed as a function of the network cost. These experimental results revealed abnormal cortical thickness and correlations in attention deficit/hyperactivity disorder, and showed that the brain structural networks of attention deficit/hyperactivity disorder subjects had inefficient small-world topological features. Furthermore, their topological properties were altered abnormally. In particular, decreased global efficiency combined with increased local efficiency in attention deficit/hyperactivity disorder children led to a disorder-related shift of the network topological structure toward regular networks. In addition, nodal efficiency, cortical thickness, and correlation analyses revealed that several brain regions were altered in attention deficit/hyperactivity disorder patients. These findings are in accordance with a hypothesis of dysfunctional integration and segregation of the brain in patients with attention deficit/hyperactivity disorder and provide further evidence of brain dysfunction in attention deficit/hyperactivity disorder patients by observing cortical thickness on magnetic resonance imaging.

Converging evidence for abnormalities of the prefrontal cortex and evaluation of midsagittal structures in pediatric PTSD: an MRI study

PubMed Central

Carrion, Victor G.; Weems, Carl F.; Watson, Christa; Eliez, Stephan; Menon, Vinod; Reiss, Allan L.

2009-01-01

Objective Volumetric imaging research has shown abnormal brain morphology in posttraumatic stress disorder (PTSD) when compared to controls. We present results on a study of brain morphology in the prefrontal cortex (PFC) and midline structures, via indices of gray matter volume and density, in pediatric PTSD. We hypothesized that both methods would demonstrate aberrant morphology in the PFC. Further, we hypothesized aberrant brainstem anatomy and reduced corpus collosum volume in children with PTSD. Methods Twenty-four children (aged 7-14) with history of interpersonal trauma and 24 age, and gender matched controls underwent structural magnetic resonance imaging. Images of the PFC and midline brain structures were first analyzed using volumetric image analysis. The PFC data were then compared with whole-brain voxel-based techniques using statistical parametric mapping (SPM). Results The PTSD group showed significant increased gray matter volume in the right and left inferior and superior quadrants of the prefrontal cortex and smaller gray matter volume in pons, and posterior vermis areas by volumetric image analysis. The voxel-byvoxel group comparisons demonstrated increased gray matter density mostly localized to ventral PFC as compared to the control group. Conclusions Abnormal frontal lobe morphology, as revealed by separate-complementary image analysis methods, and reduced pons and posterior vermis areas are associated with pediatric PTSD. Voxel-based morphometry may help to corroborate and further localize data obtained by volume of interest methods in PTSD. PMID:19349151

Brain MRI Tumor Detection using Active Contour Model and Local Image Fitting Energy

NASA Astrophysics Data System (ADS)

Nabizadeh, Nooshin; John, Nigel

2014-03-01

Automatic abnormality detection in Magnetic Resonance Imaging (MRI) is an important issue in many diagnostic and therapeutic applications. Here an automatic brain tumor detection method is introduced that uses T1-weighted images and K. Zhang et. al.'s active contour model driven by local image fitting (LIF) energy. Local image fitting energy obtains the local image information, which enables the algorithm to segment images with intensity inhomogeneities. Advantage of this method is that the LIF energy functional has less computational complexity than the local binary fitting (LBF) energy functional; moreover, it maintains the sub-pixel accuracy and boundary regularization properties. In Zhang's algorithm, a new level set method based on Gaussian filtering is used to implement the variational formulation, which is not only vigorous to prevent the energy functional from being trapped into local minimum, but also effective in keeping the level set function regular. Experiments show that the proposed method achieves high accuracy brain tumor segmentation results.

Oligoclonal banding of IgG in CSF, blood-brain barrier function, and MRI findings in patients with sarcoidosis, systemic lupus erythematosus, and Behçet's disease involving the nervous system.

PubMed Central

McLean, B N; Miller, D; Thompson, E J

1995-01-01

A retrospective study of CSF and serum analysis from a total of 43 patients with sarcoidosis, 20 with systemic lupus erythematosus, and 12 with Behçet's disease with neurological involvement found local synthesis of oligoclonal IgG using isoelectric focusing and immunoblotting in 51%, 25%, and 8% respectively at some stage in their disease. Blood-brain barrier breakdown, when assessed with an albumin ratio found 47% of patients with sarcoidosis, 30% of those with systemic lupus erythematosus, and 42% of patients with Behçet's disease exhibiting abnormal barrier function at some time. Serial CSF analysis showed that clinical relapses were associated with worsening barrier function and in some patients the development of local oligoclonal IgG synthesis; conversely steroid treatment led to a statistically significant improvement in barrier function, and in two patients a loss of oligoclonal IgG bands. A higher proportion of patients had MRI abnormalities than oligoclonal IgG or blood-brain barrier breakdown, MRI being abnormal in 16 of 19 patients with sarcoidosis, three of four patients with systemic lupus erythematosus, and seven of nine patients with Behçet's disease, although this may have been due to temporal factors. In the differential diagnosis of chronic neurological disorders, locally synthesised oligoclonal IgG cannot distinguish between diseases, but the loss of bands seen in two patients contrasts with what is seen in multiple sclerosis, and thus may be a useful diagnostic clue. PMID:7745401

Abnormally increased and incoherent resting-state activity is shared between patients with schizophrenia and their unaffected siblings.

PubMed

Liu, Chang; Xue, Zhimin; Palaniyappan, Lena; Zhou, Li; Liu, Haihong; Qi, Chang; Wu, Guowei; Mwansisya, Tumbwene E; Tao, Haojuan; Chen, Xudong; Huang, Xiaojun; Liu, Zhening; Pu, Weidan

2016-03-01

Several resting-state neuroimaging studies in schizophrenia indicate an excessive brain activity while others report an incoherent brain activity at rest. No direct evidence for the simultaneous presence of both excessive and incoherent brain activity has been established to date. Moreover, it is unclear whether unaffected siblings of schizophrenia patients who share half of the affected patient's genotype also exhibit the excessive and incoherent brain activity that may render them vulnerable to the development of schizophrenia. 27 pairs of schizophrenia patients and their unaffected siblings, as well as 27 healthy controls, were scanned using gradient-echo echo-planar imaging at rest. By using amplitude of low-frequency fluctuations (ALFF) and regional homogeneity (Reho), we investigated the intensity and synchronization of local spontaneous neuronal activity in three groups. We observed that increased amplitude and reduced synchronization (coherence) of spontaneous neuronal activity were shared by patients and their unaffected siblings. The key brain regions with this abnormal neural pattern in both patients and siblings included the middle temporal, orbito-frontal, inferior occipital and fronto-insular gyrus. This abnormal neural pattern of excessive and incoherent neuronal activity shared by schizophrenia patients and their healthy siblings may improve our understanding of neuropathology and genetic predisposition in schizophrenia. Copyright © 2016 Elsevier B.V. All rights reserved.

Support Vector Machine Classification of Major Depressive Disorder Using Diffusion-Weighted Neuroimaging and Graph Theory

PubMed Central

Sacchet, Matthew D.; Prasad, Gautam; Foland-Ross, Lara C.; Thompson, Paul M.; Gotlib, Ian H.

2015-01-01

Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on “support vector machines” to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities. PMID:25762941

Support vector machine classification of major depressive disorder using diffusion-weighted neuroimaging and graph theory.

PubMed

Sacchet, Matthew D; Prasad, Gautam; Foland-Ross, Lara C; Thompson, Paul M; Gotlib, Ian H

2015-01-01

Recently, there has been considerable interest in understanding brain networks in major depressive disorder (MDD). Neural pathways can be tracked in the living brain using diffusion-weighted imaging (DWI); graph theory can then be used to study properties of the resulting fiber networks. To date, global abnormalities have not been reported in tractography-based graph metrics in MDD, so we used a machine learning approach based on "support vector machines" to differentiate depressed from healthy individuals based on multiple brain network properties. We also assessed how important specific graph metrics were for this differentiation. Finally, we conducted a local graph analysis to identify abnormal connectivity at specific nodes of the network. We were able to classify depression using whole-brain graph metrics. Small-worldness was the most useful graph metric for classification. The right pars orbitalis, right inferior parietal cortex, and left rostral anterior cingulate all showed abnormal network connectivity in MDD. This is the first use of structural global graph metrics to classify depressed individuals. These findings highlight the importance of future research to understand network properties in depression across imaging modalities, improve classification results, and relate network alterations to psychiatric symptoms, medication, and comorbidities.

A mutation in Ccdc39 causes neonatal hydrocephalus with abnormal motile cilia development in mice.

PubMed

Abdelhamed, Zakia; Vuong, Shawn M; Hill, Lauren; Shula, Crystal; Timms, Andrew; Beier, David; Campbell, Kenneth; Mangano, Francesco T; Stottmann, Rolf W; Goto, June

2018-01-09

Pediatric hydrocephalus is characterized by an abnormal accumulation of cerebrospinal fluid (CSF) and is one of the most common congenital brain abnormalities. However, little is known about the molecular and cellular mechanisms regulating CSF flow in the developing brain. Through whole-genome sequencing analysis, we report that a homozygous splice site mutation in coiled-coil domain containing 39 ( Ccdc39 ) is responsible for early postnatal hydrocephalus in the progressive hydrocephal us ( prh ) mouse mutant. Ccdc39 is selectively expressed in embryonic choroid plexus and ependymal cells on the medial wall of the forebrain ventricle, and the protein is localized to the axoneme of motile cilia. The Ccdc39 prh/prh ependymal cells develop shorter cilia with disorganized microtubules lacking the axonemal inner arm dynein. Using high-speed video microscopy, we show that an orchestrated ependymal ciliary beating pattern controls unidirectional CSF flow on the ventricular surface, which generates bulk CSF flow in the developing brain. Collectively, our data provide the first evidence for involvement of Ccdc39 in hydrocephalus and suggest that the proper development of medial wall ependymal cilia is crucial for normal mouse brain development. © 2018. Published by The Company of Biologists Ltd.

Glucose Metabolism during Resting State Reveals Abnormal Brain Networks Organization in the Alzheimer’s Disease and Mild Cognitive Impairment

PubMed Central

Martínez-Montes, Eduardo

2013-01-01

This paper aims to study the abnormal patterns of brain glucose metabolism co-variations in Alzheimer disease (AD) and Mild Cognitive Impairment (MCI) patients compared to Normal healthy controls (NC) using the Alzheimer Disease Neuroimaging Initiative (ADNI) database. The local cerebral metabolic rate for glucose (CMRgl) in a set of 90 structures belonging to the AAL atlas was obtained from Fluro-Deoxyglucose Positron Emission Tomography data in resting state. It is assumed that brain regions whose CMRgl values are significantly correlated are functionally associated; therefore, when metabolism is altered in a single region, the alteration will affect the metabolism of other brain areas with which it interrelates. The glucose metabolism network (represented by the matrix of the CMRgl co-variations among all pairs of structures) was studied using the graph theory framework. The highest concurrent fluctuations in CMRgl were basically identified between homologous cortical regions in all groups. Significant differences in CMRgl co-variations in AD and MCI groups as compared to NC were found. The AD and MCI patients showed aberrant patterns in comparison to NC subjects, as detected by global and local network properties (global and local efficiency, clustering index, and others). MCI network’s attributes showed an intermediate position between NC and AD, corroborating it as a transitional stage from normal aging to Alzheimer disease. Our study is an attempt at exploring the complex association between glucose metabolism, CMRgl covariations and the attributes of the brain network organization in AD and MCI. PMID:23894356

Preserved local but disrupted contextual figure-ground influences in an individual with abnormal function of intermediate visual areas

PubMed Central

Brooks, Joseph L.; Gilaie-Dotan, Sharon; Rees, Geraint; Bentin, Shlomo; Driver, Jon

2012-01-01

Visual perception depends not only on local stimulus features but also on their relationship to the surrounding stimulus context, as evident in both local and contextual influences on figure-ground segmentation. Intermediate visual areas may play a role in such contextual influences, as we tested here by examining LG, a rare case of developmental visual agnosia. LG has no evident abnormality of brain structure and functional neuroimaging showed relatively normal V1 function, but his intermediate visual areas (V2/V3) function abnormally. We found that contextual influences on figure-ground organization were selectively disrupted in LG, while local sources of figure-ground influences were preserved. Effects of object knowledge and familiarity on figure-ground organization were also significantly diminished. Our results suggest that the mechanisms mediating contextual and familiarity influences on figure-ground organization are dissociable from those mediating local influences on figure-ground assignment. The disruption of contextual processing in intermediate visual areas may play a role in the substantial object recognition difficulties experienced by LG. PMID:22947116

Scan-stratified case-control sampling for modeling blood-brain barrier integrity in multiple sclerosis.

PubMed

Pomann, Gina-Maria; Sweeney, Elizabeth M; Reich, Daniel S; Staicu, Ana-Maria; Shinohara, Russell T

2015-09-10

Multiple sclerosis (MS) is an immune-mediated neurological disease that causes morbidity and disability. In patients with MS, the accumulation of lesions in the white matter of the brain is associated with disease progression and worse clinical outcomes. Breakdown of the blood-brain barrier in newer lesions is indicative of more active disease-related processes and is a primary outcome considered in clinical trials of treatments for MS. Such abnormalities in active MS lesions are evaluated in vivo using contrast-enhanced structural MRI, during which patients receive an intravenous infusion of a costly magnetic contrast agent. In some instances, the contrast agents can have toxic effects. Recently, local image regression techniques have been shown to have modest performance for assessing the integrity of the blood-brain barrier based on imaging without contrast agents. These models have centered on the problem of cross-sectional classification in which patients are imaged at a single study visit and pre-contrast images are used to predict post-contrast imaging. In this paper, we extend these methods to incorporate historical imaging information, and we find the proposed model to exhibit improved performance. We further develop scan-stratified case-control sampling techniques that reduce the computational burden of local image regression models, while respecting the low proportion of the brain that exhibits abnormal vascular permeability. Copyright © 2015 John Wiley & Sons, Ltd.

Altered regional homogeneity in patients with late monocular blindness: a resting-state functional MRI study

PubMed Central

Huang, Xin; Ye, Cheng-Long; Zhong, Yu-Lin; Ye, Lei; Yang, Qi-Chen; Li, Hai-Jun; Jiang, Nan; Peng, De-Chang

2017-01-01

Many previous studies have demonstrated that the blindness patients have has functional and anatomical abnormalities in the visual and other vision-related cortex. However, changes in the brain function in late monocular blindness (MB) at rest are largely unknown. In this study, we investigated the underlying regional homogeneity (ReHo) of brain-activity abnormalities in patients with late MB and their relationship with clinical features. A total of 32 patients with MB (25 male and seven female) and 32 healthy controls (HCs) (25 male and seven female) closely matched in age, sex, and education underwent resting-state functional MRI scans. The ReHo method was used to assess local features of spontaneous brain activities. Patients with MB were distinguishable from HCs using the receiver operating characteristic curve. The relationship between the mean ReHo in brain regions and the behavioral performance was calculated using correlation analysis. Compared with HCs, patients with MB showed significantly decreased ReHo values in the right rectal gyrus, right cuneus, right anterior cingulate, and right lateral occipital cortex and increased ReHo values in the right inferior temporal gyrus, right frontal middle orbital, left posterior cingulate/precuneus, and left middle frontal gyrus. However, there was no significant relationship between the different mean ReHo values in the brain regions and the clinical features. Late MB involves abnormalities of the visual cortex and other vision-related brain regions, which may reflect brain dysfunction in these regions. PMID:28858036

Whole-brain functional connectivity identification of functional dyspepsia.

PubMed

Nan, Jiaofen; Liu, Jixin; Li, Guoying; Xiong, Shiwei; Yan, Xuemei; Yin, Qing; Zeng, Fang; von Deneen, Karen M; Liang, Fanrong; Gong, Qiyong; Qin, Wei; Tian, Jie

2013-01-01

Recent neuroimaging studies have shown local brain aberrations in functional dyspepsia (FD) patients, yet little attention has been paid to the whole-brain resting-state functional network abnormalities. The purpose of this study was to investigate whether FD disrupts the patterns of whole-brain networks and the abnormal functional connectivity could reflect the severity of the disease. The dysfunctional interactions between brain regions at rest were investigated in FD patients as compared with 40 age- and gender- matched healthy controls. Multivariate pattern analysis was used to evaluate the discriminative power of our results for classifying patients from controls. In our findings, the abnormal brain functional connections were mainly situated within or across the limbic/paralimbic system, the prefrontal cortex, the tempo-parietal areas and the visual cortex. About 96% of the subjects among the original dataset were correctly classified by a leave one-out cross-validation approach, and 88% accuracy was also validated in a replication dataset. The classification features were significantly associated with the patients' dyspepsia symptoms, the self-rating depression scale and self-rating anxiety scale, but it was not correlated with duration of FD patients (p>0.05). Our results may indicate the effectiveness of the altered brain functional connections reflecting the disease pathophysiology underling FD. These dysfunctional connections may be the epiphenomena or causative agents of FD, which may be affected by clinical severity and its related emotional dimension of the disease rather than the clinical course.

Maturational trajectories of local and long-range functional connectivity in autism during face processing.

PubMed

Mamashli, Fahimeh; Khan, Sheraz; Bharadwaj, Hari; Losh, Ainsley; Pawlyszyn, Stephanie M; Hämäläinen, Matti S; Kenet, Tal

2018-06-26

Autism spectrum disorder (ASD) is characterized neurophysiologically by, among other things, functional connectivity abnormalities in the brain. Recent evidence suggests that the nature of these functional connectivity abnormalities might not be uniform throughout maturation. Comparing between adolescents and young adults (ages 14-21) with ASD and age- and IQ-matched typically developing (TD) individuals, we previously documented, using magnetoencephalography (MEG) data, that local functional connectivity in the fusiform face areas (FFA) and long-range functional connectivity between FFA and three higher order cortical areas were all reduced in ASD. Given the findings on abnormal maturation trajectories in ASD, we tested whether these results extend to preadolescent children (ages 7-13). We found that both local and long-range functional connectivity were in fact normal in this younger age group in ASD. Combining the two age groups, we found that local and long-range functional connectivity measures were positively correlated with age in TD, but negatively correlated with age in ASD. Last, we showed that local functional connectivity was the primary feature in predicting age in ASD group, but not in the TD group. Furthermore, local functional connectivity was only correlated with ASD severity in the older group. These results suggest that the direction of maturation of functional connectivity for processing of faces from childhood to young adulthood is itself abnormal in ASD, and that during the processing of faces, these trajectory abnormalities are more pronounced for local functional connectivity measures than they are for long-range functional connectivity measures. © 2018 Wiley Periodicals, Inc.

The effect of selective tibial neurotomy and rehabilitation in a quadriplegic patient with ankle spasticity following traumatic brain injury.

PubMed

Jang, Sung Ho; Park, Sung-Min; Kim, Seong Ho; Ahn, Sang Ho; Cho, Yun Woo; Ahn, Mi Ok

2004-08-31

Ankle spasticity following brain injury leads to abnormal posture and joint contracture; making standing or walking impossible. This study investigates the efficacy of selective tibial neurotomy (STN) and intensive rehabilitation in a patient who suffered ankle spasticity after brain injury. This case describes a 37-year-old man whose traumatic brain injury (TBI) resulted in severe right ankle spasticity and contracture. He was unable to stand due to severe right ankle spasticity and contracture. Intensive rehabilitation and STN allowed him to walk without brace at 6 months and run at 12 months after STN. STN is an effective procedure to resolve localized spasticity of the ankle and it may be considered as a management strategy after local injection to alleviate ankle spasticity and/or contracture prior to orthopaedic surgery.

Alterations in brain temperatures as a possible cause of migraine headache.

PubMed

Horváth, Csilla

2014-05-01

Migraine is a debilitating disease with a recurring generally unilateral headache and concomitant symptoms of nausea, vomiting and photo- and/or phonophobia that affects some 11-18% of the population. Most of the mechanisms previously put forward to explain the attacks have been questioned or give an explanation only some of the symptoms. Moreover, the best drugs for treatment are still the 20-year-old triptans, which have serious limitations as regards both efficacy and tolerability. As the dura and some cranial vessels are the only intracranial structures capable of pain sensations, a vascular theory of migraine emerged, but has been debated. Recent theories identified the hyperexcitability of structures involved in pain transmission, such as the trigeminal system or the cortex, or an abnormal modulatory function of the brainstem. However, there is ongoing scientific debate concerning these theories, neither of which is fully capable of explaining the occurrence of a migraine attack. The present article puts forward a hypothesis of the possibility of abnormal temperature regulation in certain regions or the overall brain in migraineurs, the attack being a defense mechanism to prevent neuronal damage. Few examinations have been made of temperature regulation in the human brain. It lacks the carotid rete, a vascular heat exchanger that serves in many animals to provide constant brain temperature. The human brain contains a high density of neurons with a considerable energy demand that is converted to heat. The human brain has a higher temperature than other parts of the body and needs continuous cooling. Recent studies revealed unexpectedly great variations in temperature of various structures of the brain and considerable changes in response to functional activation. There is various evidence in support of the hypothesis that accumulated heat in some structure or the overall brain may be behind the symptoms observed, such as a platelet abnormality, a decreased serotonin content, and dural "inflammation" including vasodilation and brainstem activation. The hypothesis postulates that a migraine attack serves to restore the brain temperature. Abnormally low temperatures in the brain can also result in headache. Surprisingly, no systematic examination of brain temperature changes in migraineurs has been published. Certain case reports support the present hypothesis. Various noninvasive technologies (e.g. MR) capable of monitoring brain temperature are available. If a systematic examination of local brain temperature revealed abnormalities in structures presumed to be involved in migraine, that would increase our understanding of the disease and trigger the development of improved treatment. Copyright © 2014 Elsevier Ltd. All rights reserved.

Functional brain abnormalities in major depressive disorder using the Hilbert-Huang transform.

PubMed

Yu, Haibin; Li, Feng; Wu, Tong; Li, Rui; Yao, Li; Wang, Chuanyue; Wu, Xia

2018-02-09

Major depressive disorder is a common disease worldwide, which is characterized by significant and persistent depression. Non-invasive accessory diagnosis of depression can be performed by resting-state functional magnetic resonance imaging (rs-fMRI). However, the fMRI signal may not satisfy linearity and stationarity. The Hilbert-Huang transform (HHT) is an adaptive time-frequency localization analysis method suitable for nonlinear and non-stationary signals. The objective of this study was to apply the HHT to rs-fMRI to find the abnormal brain areas of patients with depression. A total of 35 patients with depression and 37 healthy controls were subjected to rs-fMRI. The HHT was performed to extract the Hilbert-weighted mean frequency of the rs-fMRI signals, and multivariate receiver operating characteristic analysis was applied to find the abnormal brain regions with high sensitivity and specificity. We observed differences in Hilbert-weighted mean frequency between the patients and healthy controls mainly in the right hippocampus, right parahippocampal gyrus, left amygdala, and left and right caudate nucleus. Subsequently, the above-mentioned regions were included in the results obtained from the compared region homogeneity and the fractional amplitude of low frequency fluctuation method. We found brain regions with differences in the Hilbert-weighted mean frequency, and examined their sensitivity and specificity, which suggested a potential neuroimaging biomarker to distinguish between patients with depression and healthy controls. We further clarified the pathophysiological abnormality of these regions for the population with major depressive disorder.

Maladaptive Neural Synchrony in Tinnitus: Origin and Restoration

PubMed Central

Eggermont, Jos J.; Tass, Peter A.

2015-01-01

Tinnitus is the conscious perception of sound heard in the absence of physical sound sources external or internal to the body, reflected in aberrant neural synchrony of spontaneous or resting-state brain activity. Neural synchrony is generated by the nearly simultaneous firing of individual neurons, of the synchronization of membrane-potential changes in local neural groups as reflected in the local field potentials, resulting in the presence of oscillatory brain waves in the EEG. Noise-induced hearing loss, often resulting in tinnitus, causes a reorganization of the tonotopic map in auditory cortex and increased spontaneous firing rates and neural synchrony. Spontaneous brain rhythms rely on neural synchrony. Abnormal neural synchrony in tinnitus appears to be confined to specific frequency bands of brain rhythms. Increases in delta-band activity are generated by deafferented/deprived neuronal networks resulting from hearing loss. Coordinated reset (CR) stimulation was developed in order to specifically counteract such abnormal neuronal synchrony by desynchronization. The goal of acoustic CR neuromodulation is to desynchronize tinnitus-related abnormal delta-band oscillations. CR neuromodulation does not require permanent stimulus delivery in order to achieve long-lasting desynchronization or even a full-blown anti-kindling but may have cumulative effects, i.e., the effect of different CR epochs separated by pauses may accumulate. Unlike other approaches, acoustic CR neuromodulation does not intend to reduce tinnitus-related neuronal activity by employing lateral inhibition. The potential efficacy of acoustic CR modulation was shown in a clinical proof of concept trial, where effects achieved in 12 weeks of treatment delivered 4–6 h/day persisted through a preplanned 4-week therapy pause and showed sustained long-term effects after 10 months of therapy, leading to 75% responders. PMID:25741316

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training

PubMed Central

Sherwood, Matthew S.; Diller, Emily E.; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T.; Parker, Jason G.

2017-01-01

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain. PMID:28872110

A Protocol for the Administration of Real-Time fMRI Neurofeedback Training.

PubMed

Sherwood, Matthew S; Diller, Emily E; Ey, Elizabeth; Ganapathy, Subhashini; Nelson, Jeremy T; Parker, Jason G

2017-08-24

Neurologic disorders are characterized by abnormal cellular-, molecular-, and circuit-level functions in the brain. New methods to induce and control neuroplastic processes and correct abnormal function, or even shift functions from damaged tissue to physiologically healthy brain regions, hold the potential to dramatically improve overall health. Of the current neuroplastic interventions in development, neurofeedback training (NFT) from functional Magnetic Resonance Imaging (fMRI) has the advantages of being completely non-invasive, non-pharmacologic, and spatially localized to target brain regions, as well as having no known side effects. Furthermore, NFT techniques, initially developed using fMRI, can often be translated to exercises that can be performed outside of the scanner without the aid of medical professionals or sophisticated medical equipment. In fMRI NFT, the fMRI signal is measured from specific regions of the brain, processed, and presented to the participant in real-time. Through training, self-directed mental processing techniques, that regulate this signal and its underlying neurophysiologic correlates, are developed. FMRI NFT has been used to train volitional control over a wide range of brain regions with implications for several different cognitive, behavioral, and motor systems. Additionally, fMRI NFT has shown promise in a broad range of applications such as the treatment of neurologic disorders and the augmentation of baseline human performance. In this article, we present an fMRI NFT protocol developed at our institution for modulation of both healthy and abnormal brain function, as well as examples of using the method to target both cognitive and auditory regions of the brain.

Altered spontaneous brain activity in adolescent boys with pure conduct disorder revealed by regional homogeneity analysis.

PubMed

Wu, Qiong; Zhang, Xiaocui; Dong, Daifeng; Wang, Xiang; Yao, Shuqiao

2017-07-01

Functional magnetic resonance imaging (fMRI) studies have revealed abnormal neural activity in several brain regions of adolescents with conduct disorder (CD) performing various tasks. However, little is known about the spontaneous neural activity in people with CD in a resting state. The aims of this study were to investigate CD-associated regional activity abnormalities and to explore the relationship between behavioral impulsivity and regional activity abnormalities. Resting-state fMRI (rs-fMRI) scans were administered to 28 adolescents with CD and 28 age-, gender-, and IQ-matched healthy controls (HCs). The rs-fMRI data were subjected to regional homogeneity (ReHo) analysis. ReHo can demonstrate the temporal synchrony of regional blood oxygen level-dependent signals and reflect the coordination of local neuronal activity facilitating similar goals or representations. Compared to HCs, the CD group showed increased ReHo bilaterally in the insula as well as decreased ReHo in the right inferior parietal lobule, right middle temporal gyrus and right fusiform gyrus, left anterior cerebellum anterior, and right posterior cerebellum. In the CD group, mean ReHo values in the left and the right insula correlated positively with Barratt Impulsivity Scale (BIS) total scores. The results suggest that CD is associated with abnormal intrinsic brain activity, mainly in the cerebellum and temporal-parietal-limbic cortices, regions that are related to emotional and cognitive processing. BIS scores in adolescents with CD may reflect severity of abnormal neuronal synchronization in the insula.

Gadolinium Deposition in Human Brain Tissues after Contrast-enhanced MR Imaging in Adult Patients without Intracranial Abnormalities.

PubMed

McDonald, Robert J; McDonald, Jennifer S; Kallmes, David F; Jentoft, Mark E; Paolini, Michael A; Murray, David L; Williamson, Eric E; Eckel, Laurence J

2017-11-01

Purpose To determine whether gadolinium deposits in neural tissues of patients with intracranial abnormalities following intravenous gadolinium-based contrast agent (GBCA) exposure might be related to blood-brain barrier integrity by studying adult patients with normal brain pathologic characteristics. Materials and Methods After obtaining antemortem consent and institutional review board approval, the authors compared postmortem neuronal tissue samples from five patients who had undergone four to 18 gadolinium-enhanced magnetic resonance (MR) examinations between 2005 and 2014 (contrast group) with samples from 10 gadolinium-naive patients who had undergone at least one MR examination during their lifetime (control group). All patients in the contrast group had received gadodiamide. Neuronal tissues from the dentate nuclei, pons, globus pallidus, and thalamus were harvested and analyzed with inductively coupled plasma mass spectrometry (ICP-MS), transmission electron microscopy with energy-dispersive x-ray spectroscopy, and light microscopy to quantify, localize, and assess the effects of gadolinium deposition. Results Tissues from the four neuroanatomic regions of gadodiamide-exposed patients contained 0.1-19.4 μg of gadolinium per gram of tissue in a statistically significant dose-dependent relationship (globus pallidus: ρ = 0.90, P = .04). In contradistinction, patients in the control group had undetectable levels of gadolinium with ICP-MS. All patients had normal brain pathologic characteristics at autopsy. Three patients in the contrast group had borderline renal function (estimated glomerular filtration rate <45 mL/min/1.73 m 2 ) and hepatobiliary dysfunction at MR examination. Gadolinium deposition in the contrast group was localized to the capillary endothelium and neuronal interstitium and, in two cases, within the nucleus of the cell. Conclusion Gadolinium deposition in neural tissues after GBCA administration occurs in the absence of intracranial abnormalities that might affect the permeability of the blood-brain barrier. These findings challenge current understanding of the biodistribution of these contrast agents and their safety. © RSNA, 2017.

Delayed increases in microvascular pathology after experimental traumatic brain injury are associated with prolonged inflammation, blood-brain barrier disruption, and progressive white matter damage.

PubMed

Glushakova, Olena Y; Johnson, Danny; Hayes, Ronald L

2014-07-01

Traumatic brain injury (TBI) is a significant risk factor for chronic traumatic encephalopathy (CTE), Alzheimer's disease (AD), and Parkinson's disease (PD). Cerebral microbleeds, focal inflammation, and white matter damage are associated with many neurological and neurodegenerative disorders including CTE, AD, PD, vascular dementia, stroke, and TBI. This study evaluates microvascular abnormalities observed at acute and chronic stages following TBI in rats, and examines pathological processes associated with these abnormalities. TBI in adult rats was induced by controlled cortical impact (CCI) of two magnitudes. Brain pathology was assessed in white matter of the corpus callosum for 24 h to 3 months following injury using immunohistochemistry (IHC). TBI resulted in focal microbleeds that were related to the magnitude of injury. At the lower magnitude of injury, microbleeds gradually increased over the 3 month duration of the study. IHC revealed TBI-induced focal abnormalities including blood-brain barrier (BBB) damage (IgG), endothelial damage (intercellular adhesion molecule 1 [ICAM-1]), activation of reactive microglia (ionized calcium binding adaptor molecule 1 [Iba1]), gliosis (glial fibrillary acidic protein [GFAP]) and macrophage-mediated inflammation (cluster of differentiation 68 [CD68]), all showing different temporal profiles. At chronic stages (up to 3 months), apparent myelin loss (Luxol fast blue) and scattered deposition of microbleeds were observed. Microbleeds were surrounded by glial scars and co-localized with CD68 and IgG puncta stainings, suggesting that localized BBB breakdown and inflammation were associated with vascular damage. Our results indicate that evolving white matter degeneration following experimental TBI is associated with significantly delayed microvascular damage and focal microbleeds that are temporally and regionally associated with development of punctate BBB breakdown and progressive inflammatory responses. Increased understanding of mechanisms underlying delayed microvascular damage following TBI could provide novel insights into chronic pathological responses to TBI and potential common mechanisms underlying TBI and neurodegenerative diseases.

Prevalence of prenatal brain abnormalities in fetuses with congenital heart disease: a systematic review.

PubMed

Khalil, A; Bennet, S; Thilaganathan, B; Paladini, D; Griffiths, P; Carvalho, J S

2016-09-01

Studies have shown an association between congenital heart defects (CHDs) and postnatal brain abnormalities and neurodevelopmental delay. Recent evidence suggests that some of these brain abnormalities are present before birth. The primary aim of this study was to perform a systematic review to quantify the prevalence of prenatal brain abnormalities in fetuses with CHDs. MEDLINE, EMBASE and The Cochrane Library were searched electronically. Reference lists within each article were hand-searched for additional reports. The outcomes observed included structural brain abnormalities (on magnetic resonance imaging (MRI)) and changes in brain volume (on MRI, three-dimensional (3D) volumetric MRI, 3D ultrasound and phase-contrast MRI), brain metabolism or maturation (on magnetic resonance spectroscopy and phase-contrast MRI) and brain blood flow (on Doppler ultrasound, phase-contrast MRI and 3D power Doppler ultrasound) in fetuses with CHDs. Cohort and case-control studies were included and cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Proportion meta-analysis was used for analysis. Between-study heterogeneity was assessed using the I(2) test. The search yielded 1943 citations, and 20 studies (n = 1175 cases) were included in the review. Three studies reported data on structural brain abnormalities, while data on altered brain volume, metabolism and blood flow were reported in seven, three and 14 studies, respectively. The three studies (221 cases) reporting on structural brain abnormalities were suitable for inclusion in a meta-analysis. The prevalence of prenatal structural brain abnormalities in fetuses with CHD was 28% (95% CI, 18-40%), with a similar prevalence (25% (95% CI, 14-39%)) when tetralogy of Fallot was considered alone. These abnormalities included ventriculomegaly (most common), agenesis of the corpus callosum, ventricular bleeding, increased extra-axial space, vermian hypoplasia, white-matter abnormalities and delayed brain development. Fetuses with CHD were more likely than those without CHD to have reduced brain volume, delay in brain maturation and altered brain circulation, most commonly in the form of reduced middle cerebral artery pulsatility index and cerebroplacental ratio. These changes were usually evident in the third trimester, but some studies reported them from as early as the second trimester. In the absence of known major aneuploidy or genetic syndromes, fetuses with CHD are at increased risk of brain abnormalities, which are discernible prenatally. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2016 ISUOG. Published by John Wiley & Sons Ltd.

Birth Defects Among Fetuses and Infants of US Women With Evidence of Possible Zika Virus Infection During Pregnancy.

PubMed

Honein, Margaret A; Dawson, April L; Petersen, Emily E; Jones, Abbey M; Lee, Ellen H; Yazdy, Mahsa M; Ahmad, Nina; Macdonald, Jennifer; Evert, Nicole; Bingham, Andrea; Ellington, Sascha R; Shapiro-Mendoza, Carrie K; Oduyebo, Titilope; Fine, Anne D; Brown, Catherine M; Sommer, Jamie N; Gupta, Jyoti; Cavicchia, Philip; Slavinski, Sally; White, Jennifer L; Owen, S Michele; Petersen, Lyle R; Boyle, Coleen; Meaney-Delman, Dana; Jamieson, Denise J

2017-01-03

Understanding the risk of birth defects associated with Zika virus infection during pregnancy may help guide communication, prevention, and planning efforts. In the absence of Zika virus, microcephaly occurs in approximately 7 per 10 000 live births. To estimate the preliminary proportion of fetuses or infants with birth defects after maternal Zika virus infection by trimester of infection and maternal symptoms. Completed pregnancies with maternal, fetal, or infant laboratory evidence of possible recent Zika virus infection and outcomes reported in the continental United States and Hawaii from January 15 to September 22, 2016, in the US Zika Pregnancy Registry, a collaboration between the CDC and state and local health departments. Laboratory evidence of possible recent Zika virus infection in a maternal, placental, fetal, or infant sample. Birth defects potentially Zika associated: brain abnormalities with or without microcephaly, neural tube defects and other early brain malformations, eye abnormalities, and other central nervous system consequences. Among 442 completed pregnancies in women (median age, 28 years; range, 15-50 years) with laboratory evidence of possible recent Zika virus infection, birth defects potentially related to Zika virus were identified in 26 (6%; 95% CI, 4%-8%) fetuses or infants. There were 21 infants with birth defects among 395 live births and 5 fetuses with birth defects among 47 pregnancy losses. Birth defects were reported for 16 of 271 (6%; 95% CI, 4%-9%) pregnant asymptomatic women and 10 of 167 (6%; 95% CI, 3%-11%) symptomatic pregnant women. Of the 26 affected fetuses or infants, 4 had microcephaly and no reported neuroimaging, 14 had microcephaly and brain abnormalities, and 4 had brain abnormalities without microcephaly; reported brain abnormalities included intracranial calcifications, corpus callosum abnormalities, abnormal cortical formation, cerebral atrophy, ventriculomegaly, hydrocephaly, and cerebellar abnormalities. Infants with microcephaly (18/442) represent 4% of completed pregnancies. Birth defects were reported in 9 of 85 (11%; 95% CI, 6%-19%) completed pregnancies with maternal symptoms or exposure exclusively in the first trimester (or first trimester and periconceptional period), with no reports of birth defects among fetuses or infants with prenatal exposure to Zika virus infection only in the second or third trimesters. Among pregnant women in the United States with completed pregnancies and laboratory evidence of possible recent Zika infection, 6% of fetuses or infants had evidence of Zika-associated birth defects, primarily brain abnormalities and microcephaly, whereas among women with first-trimester Zika infection, 11% of fetuses or infants had evidence of Zika-associated birth defects. These findings support the importance of screening pregnant women for Zika virus exposure.

Functional connectivity abnormalities and associated cognitive deficits in fetal alcohol Spectrum disorders (FASD).

PubMed

Wozniak, Jeffrey R; Mueller, Bryon A; Mattson, Sarah N; Coles, Claire D; Kable, Julie A; Jones, Kenneth L; Boys, Christopher J; Lim, Kelvin O; Riley, Edward P; Sowell, Elizabeth R

2017-10-01

Consistent with well-documented structural and microstructural abnormalities in prenatal alcohol exposure (PAE), recent studies suggest that functional connectivity (FC) may also be disrupted. We evaluated whole-brain FC in a large multi-site sample, examined its cognitive correlates, and explored its potential to objectively identify neurodevelopmental abnormality in individuals without definitive dysmorphic features. Included were 75 children with PAE and 68 controls from four sites. All participants had documented heavy prenatal alcohol exposure. All underwent a formal evaluation of physical anomalies and dysmorphic facial features. MRI data were collected using modified matched protocols on three platforms (Siemens, GE, and Philips). Resting-state FC was examined using whole-brain graph theory metrics to characterize each individual's connectivity. Although whole-brain FC metrics did not discriminate prenatally-exposed from unexposed overall, atypical FC (> 1 standard deviation from the grand mean) was significantly more common (2.7 times) in the PAE group vs. In a subset of 55 individuals (PAE and controls) whose dysmorphology examination could not definitively characterize them as either Fetal Alcohol Syndrome (FAS) or non-FAS, atypical FC was seen in 27 % of the PAE group, but 0 % of controls. Across participants, a 1 % difference in local network efficiency was associated with a 36 point difference in global cognitive functioning. Whole-brain FC metrics have potential to identify individuals with objective neurodevelopmental abnormalities from prenatal alcohol exposure. When applied to individuals unable to be classified as FAS or non-FAS from dysmorphology alone, these measures separate prenatally-exposed from non-exposed with high specificity.

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use

PubMed Central

2013-01-01

Background A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Methods/Design Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. Discussion We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use. PMID:24131511

Multimodal neuroimaging of frontal white matter microstructure in early phase schizophrenia: the impact of early adolescent cannabis use.

PubMed

Bernier, Denise; Cookey, Jacob; McAllindon, David; Bartha, Robert; Hanstock, Christopher C; Newman, Aaron J; Stewart, Sherry H; Tibbo, Philip G

2013-10-17

A disturbance in connectivity between different brain regions, rather than abnormalities within the separate regions themselves, could be responsible for the clinical symptoms and cognitive dysfunctions observed in schizophrenia. White matter, which comprises axons and their myelin sheaths, provides the physical foundation for functional connectivity in the brain. Myelin sheaths are located around the axons and provide insulation through the lipid membranes of oligodendrocytes. Empirical data suggests oligodendroglial dysfunction in schizophrenia, based on findings of abnormal myelin maintenance and repair in regions of deep white matter. The aim of this in vivo neuroimaging project is to assess the impact of early adolescent onset of regular cannabis use on brain white matter tissue integrity, and to differentiate this impact from the white matter abnormalities associated with schizophrenia. The ultimate goal is to determine the liability of early adolescent use of cannabis on brain white matter, in a vulnerable brain. Young adults with schizophrenia at the early stage of the illness (less than 5 years since diagnosis) will be the focus of this project. Four magnetic resonance imaging measurements will be used to assess different cellular aspects of white matter: a) diffusion tensor imaging, b) localized proton magnetic resonance spectroscopy with a focus on the neurochemical N-acetylaspartate, c) the transverse relaxation time constants of regional tissue water, d) and of N-acetylaspartate. These four neuroimaging indices will be assessed within the same brain region of interest, that is, a large white matter fibre bundle located in the frontal region, the left superior longitudinal fasciculus. We will expand our knowledge regarding current theoretical models of schizophrenia with a more comprehensive multimodal neuroimaging approach to studying the underlying cellular abnormalities of white matter, while taking into consideration the important confounding variable of early adolescent onset of regular cannabis use.

Clinical Correlation between Perverted Nystagmus and Brain MRI Abnormal Findings

PubMed Central

Han, Won-Gue; Yoon, Hee-Chul; Kim, Tae-Min; Rah, Yoon Chan

2016-01-01

Background and Objectives To analyze the clinical correlation between perverted nystagmus and brain magnetic resonance imaging (MRI) abnormal findings and to evaluate whether perverted nystagmus is clinically significant results of brain abnormal lesions or not. Subjects and Methods We performed medical charts review from January 2008 to July 2014, retrospectively. Patients who were suspected central originated vertigo at Frenzel goggles test were included among patients who visited our hospital. To investigate the correlation with nystagmus suspected central originated vertigo and brain MRI abnormal findings, we confirmed whether performing brain MRI or not. Then we exclude that patients not performed brain MRI. Results The number of patients with perverted nystagmus was 15, upbeating was 1 and down-beating was 14. Among these patients, 5 patients have brain MRI abnormal findings. However, 2 patients with MRI abnormal findings were not associated correctly with perverted nystagmus and only 3 patients with perverted nystagmus were considered central originated vertigo and further evaluation and treatment was performed by the department of neurology. Conclusions Perverted nystagmus was considered to the abnormalities at brain lesions, especially cerebellum, but neurologic symptoms and further evaluation were needed for exact diagnosis of central originated vertigo. PMID:27626081

Seizure classification in EEG signals utilizing Hilbert-Huang transform

PubMed Central

2011-01-01

Background Classification method capable of recognizing abnormal activities of the brain functionality are either brain imaging or brain signal analysis. The abnormal activity of interest in this study is characterized by a disturbance caused by changes in neuronal electrochemical activity that results in abnormal synchronous discharges. The method aims at helping physicians discriminate between healthy and seizure electroencephalographic (EEG) signals. Method Discrimination in this work is achieved by analyzing EEG signals obtained from freely accessible databases. MATLAB has been used to implement and test the proposed classification algorithm. The analysis in question presents a classification of normal and ictal activities using a feature relied on Hilbert-Huang Transform. Through this method, information related to the intrinsic functions contained in the EEG signal has been extracted to track the local amplitude and the frequency of the signal. Based on this local information, weighted frequencies are calculated and a comparison between ictal and seizure-free determinant intrinsic functions is then performed. Methods of comparison used are the t-test and the Euclidean clustering. Results The t-test results in a P-value < 0.02 and the clustering leads to accurate (94%) and specific (96%) results. The proposed method is also contrasted against the Multivariate Empirical Mode Decomposition that reaches 80% accuracy. Comparison results strengthen the contribution of this paper not only from the accuracy point of view but also with respect to its fast response and ease to use. Conclusion An original tool for EEG signal processing giving physicians the possibility to diagnose brain functionality abnormalities is presented in this paper. The proposed system bears the potential of providing several credible benefits such as fast diagnosis, high accuracy, good sensitivity and specificity, time saving and user friendly. Furthermore, the classification of mode mixing can be achieved using the extracted instantaneous information of every IMF, but it would be most likely a hard task if only the average value is used. Extra benefits of this proposed system include low cost, and ease of interface. All of that indicate the usefulness of the tool and its use as an efficient diagnostic tool. PMID:21609459

Seizure classification in EEG signals utilizing Hilbert-Huang transform.

PubMed

Oweis, Rami J; Abdulhay, Enas W

2011-05-24

Classification method capable of recognizing abnormal activities of the brain functionality are either brain imaging or brain signal analysis. The abnormal activity of interest in this study is characterized by a disturbance caused by changes in neuronal electrochemical activity that results in abnormal synchronous discharges. The method aims at helping physicians discriminate between healthy and seizure electroencephalographic (EEG) signals. Discrimination in this work is achieved by analyzing EEG signals obtained from freely accessible databases. MATLAB has been used to implement and test the proposed classification algorithm. The analysis in question presents a classification of normal and ictal activities using a feature relied on Hilbert-Huang Transform. Through this method, information related to the intrinsic functions contained in the EEG signal has been extracted to track the local amplitude and the frequency of the signal. Based on this local information, weighted frequencies are calculated and a comparison between ictal and seizure-free determinant intrinsic functions is then performed. Methods of comparison used are the t-test and the Euclidean clustering. The t-test results in a P-value < 0.02 and the clustering leads to accurate (94%) and specific (96%) results. The proposed method is also contrasted against the Multivariate Empirical Mode Decomposition that reaches 80% accuracy. Comparison results strengthen the contribution of this paper not only from the accuracy point of view but also with respect to its fast response and ease to use. An original tool for EEG signal processing giving physicians the possibility to diagnose brain functionality abnormalities is presented in this paper. The proposed system bears the potential of providing several credible benefits such as fast diagnosis, high accuracy, good sensitivity and specificity, time saving and user friendly. Furthermore, the classification of mode mixing can be achieved using the extracted instantaneous information of every IMF, but it would be most likely a hard task if only the average value is used. Extra benefits of this proposed system include low cost, and ease of interface. All of that indicate the usefulness of the tool and its use as an efficient diagnostic tool.

Brain Dysplasia Associated with Ciliary Dysfunction In Infants with Congenital Heart Disease

PubMed Central

Panigrahy, Ashok; Lee, Vincent; Ceschin, Rafael; Zuccoli, Giulio; Beluk, Nancy; Khalifa, Omar; Votava-Smith, Jodie K; DeBrunner, Mark; Munoz, Ricardo; Domnina, Yuliya; Morell, Victor; Wearden, Peter; De Toledo, Joan Sanchez; Devine, William; Zahid, Maliha; Lo, Cecilia W.

2016-01-01

Objective To test for associations between abnormal respiratory ciliary motion (CM) and brain abnormalities in infants with congenital heart disease (CHD) Study design We recruited 35 infants with CHD preoperatively and performed nasal tissue biopsy to assess respiratory CM by videomicroscopy. Cranial ultrasound and brain magnetic resonance imaging were obtained pre- and/or post-operatively and systematically reviewed for brain abnormalities. Segmentation was used to quantitate cerebrospinal fluid and regional brain volumes. Perinatal and perioperative clinical variables were collected. Results A total of 10 (28.5%) patients with CHD had abnormal CM. Abnormal CM was not associated with brain injury, but was correlated with increased extra-axial CSF volume (p<0.001), delayed brain maturation (p<0.05), and a spectrum of subtle dysplasia including the hippocampus (p<0.0078) and olfactory bulb (p<0.034). Abnormal CM was associated with higher composite dysplasia score (p<0.001) and both were correlated with elevated pre-operative serum lactate (p <0.001). Conclusion Abnormal respiratory CM in infants with CHD is associated with a spectrum of brain dysplasia. These findings suggest that ciliary defects may play a role in brain dysplasia in patients with CHD and have the potential to prognosticate neurodevelopmental risks. PMID:27574995

Glioma Selectivity of Magnetically Targeted Nanoparticles: A Role of Abnormal Tumor Hydrodynamics

PubMed Central

Chertok, Beata; David, Allan E.; Huang, Yongzhuo; Yang, Victor C.

2007-01-01

Magnetic targeting is a promising strategy for achieving localized drug delivery. Application of this strategy to treat brain tumors, however, is complicated by their deep intracranial location, since magnetic field density cannot be focused at a distance from an externally applied magnet. This study intended to examine whether, with magnetic targeting, pathological alteration in brain tumor flow dynamics could be of value in discriminating the diseased site from healthy brain. To address this question, the capture of magnetic nanoparticles was first assessed in vitro using a simple flow system under theoretically estimated glioma and normal brain flow conditions. Secondly, accumulation of nanoparticles via magnetic targeting was evaluated in vivo using 9L-glioma bearing rats. In vitro results that predicted a 7.6-fold increase in nanoparticle capture at glioma-versus contralateral brain-relevant flow rates were relatively consistent with the 9.6-fold glioma selectivity of nanoparticle accumulation over the contralateral brain observed in vivo. Based on these finding, the in vitro ratio of nanoparticle capture can be viewed as a plausible indicator of in vivo glioma selectivity. Overall, it can be concluded that the decreased blood flow rate in glioma, reflecting tumor vascular abnormalities, is an important contributor to glioma-selective nanoparticle accumulation with magnetic targeting. PMID:17628157

Altered regional homogeneity of spontaneous brain activity in idiopathic trigeminal neuralgia.

PubMed

Wang, Yanping; Zhang, Xiaoling; Guan, Qiaobing; Wan, Lihong; Yi, Yahui; Liu, Chun-Feng

2015-01-01

The pathophysiology of idiopathic trigeminal neuralgia (ITN) has conventionally been thought to be induced by neurovascular compression theory. Recent structural brain imaging evidence has suggested an additional central component for ITN pathophysiology. However, far less attention has been given to investigations of the basis of abnormal resting-state brain activity in these patients. The objective of this study was to investigate local brain activity in patients with ITN and its correlation with clinical variables of pain. Resting-state functional magnetic resonance imaging data from 17 patients with ITN and 19 age- and sex-matched healthy controls were analyzed using regional homogeneity (ReHo) analysis, which is a data-driven approach used to measure the regional synchronization of spontaneous brain activity. Patients with ITN had decreased ReHo in the left amygdala, right parahippocampal gyrus, and left cerebellum and increased ReHo in the right inferior temporal gyrus, right thalamus, right inferior parietal lobule, and left postcentral gyrus (corrected). Furthermore, the increase in ReHo in the left precentral gyrus was positively correlated with visual analog scale (r=0.54; P=0.002). Our study found abnormal functional homogeneity of intrinsic brain activity in several regions in ITN, suggesting the maladaptivity of the process of daily pain attacks and a central role for the pathophysiology of ITN.

Abnormalities in Structural Covariance of Cortical Gyrification in Parkinson's Disease.

PubMed

Xu, Jinping; Zhang, Jiuquan; Zhang, Jinlei; Wang, Yue; Zhang, Yanling; Wang, Jian; Li, Guanglin; Hu, Qingmao; Zhang, Yuanchao

2017-01-01

Although abnormal cortical morphology and connectivity between brain regions (structural covariance) have been reported in Parkinson's disease (PD), the topological organizations of large-scale structural brain networks are still poorly understood. In this study, we investigated large-scale structural brain networks in a sample of 37 PD patients and 34 healthy controls (HC) by assessing the structural covariance of cortical gyrification with local gyrification index (lGI). We demonstrated prominent small-world properties of the structural brain networks for both groups. Compared with the HC group, PD patients showed significantly increased integrated characteristic path length and integrated clustering coefficient, as well as decreased integrated global efficiency in structural brain networks. Distinct distributions of hub regions were identified between the two groups, showing more hub regions in the frontal cortex in PD patients. Moreover, the modular analyses revealed significantly decreased integrated regional efficiency in lateral Fronto-Insula-Temporal module, and increased integrated regional efficiency in Parieto-Temporal module in the PD group as compared to the HC group. In summary, our study demonstrated altered topological properties of structural networks at a global, regional and modular level in PD patients. These findings suggests that the structural networks of PD patients have a suboptimal topological organization, resulting in less effective integration of information between brain regions.

Glioma selectivity of magnetically targeted nanoparticles: a role of abnormal tumor hydrodynamics.

PubMed

Chertok, Beata; David, Allan E; Huang, Yongzhuo; Yang, Victor C

2007-10-08

Magnetic targeting is a promising strategy for achieving localized drug delivery. Application of this strategy to treat brain tumors, however, is complicated by their deep intracranial location, since magnetic field density cannot be focused at a distance from an externally applied magnet. This study intended to examine whether, with magnetic targeting, pathological alteration in brain tumor flow dynamics could be of value in discriminating the diseased site from healthy brain. To address this question, the capture of magnetic nanoparticles was first assessed in vitro using a simple flow system under theoretically estimated glioma and normal brain flow conditions. Secondly, accumulation of nanoparticles via magnetic targeting was evaluated in vivo using 9L-glioma bearing rats. In vitro results that predicted a 7.6-fold increase in nanoparticle capture at glioma- versus contralateral brain-relevant flow rates were relatively consistent with the 9.6-fold glioma selectivity of nanoparticle accumulation over the contralateral brain observed in vivo. Based on these finding, the in vitro ratio of nanoparticle capture can be viewed as a plausible indicator of in vivo glioma selectivity. Overall, it can be concluded that the decreased blood flow rate in glioma, reflecting tumor vascular abnormalities, is an important contributor to glioma-selective nanoparticle accumulation with magnetic targeting.

Preliminary evidence of white matter abnormality in the uncinate fasciculus in generalized social anxiety disorder.

PubMed

Phan, K Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F; Liberzon, Israel; Arfanakis, Konstantinos

2009-10-01

Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala's response to threat. The goal of this study was to investigate brain frontal WM abnormalities using diffusion tensor imaging (DTI) in patients with social anxiety disorder. A Turboprop DTI sequence was used to acquire diffusion tensor images in 30 patients with GSAD and 30 matched healthy control subjects. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects, and an automated voxel-based, whole-brain method was used to analyze group differences. Compared with healthy control subjects, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD, which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness.

Neural network topology in ADHD; evidence for maturational delay and default-mode network alterations.

PubMed

Janssen, T W P; Hillebrand, A; Gouw, A; Geladé, K; Van Mourik, R; Maras, A; Oosterlaan, J

2017-11-01

Attention-deficit/hyperactivity disorder (ADHD) has been associated with widespread brain abnormalities in white and grey matter, affecting not only local, but global functional networks as well. In this study, we explored these functional networks using source-reconstructed electroencephalography in ADHD and typically developing (TD) children. We expected evidence for maturational delay, with underlying abnormalities in the default mode network. Electroencephalograms were recorded in ADHD (n=42) and TD (n=43) during rest, and functional connectivity (phase lag index) and graph (minimum spanning tree) parameters were derived. Dependent variables were global and local network metrics in theta, alpha and beta bands. We found evidence for a more centralized functional network in ADHD compared to TD children, with decreased diameter in the alpha band (η p 2 =0.06) and increased leaf fraction (η p 2 =0.11 and 0.08) in the alpha and beta bands, with underlying abnormalities in hub regions of the brain, including default mode network. The finding of a more centralized network is in line with maturational delay models of ADHD and should be replicated in longitudinal designs. This study contributes to the literature by combining high temporal and spatial resolution to construct EEG network topology, and associates maturational-delay and default-mode interference hypotheses of ADHD. Copyright © 2017 International Federation of Clinical Neurophysiology. Published by Elsevier B.V. All rights reserved.

Luria revisited: cognitive research in schizophrenia, past implications and future challenges.

PubMed

Zaytseva, Yuliya; Chan, Raymond C K; Pöppel, Ernst; Heinz, Andreas

2015-02-27

Contemporary psychiatry is becoming more biologically oriented in the attempt to elicit a biological rationale of mental diseases. Although mental disorders comprise mostly functional abnormalities, there is a substantial overlap between neurology and psychiatry in addressing cognitive disturbances. In schizophrenia, the presence of cognitive impairment prior to the onset of psychosis and early after its manifestation suggests that some neurocognitive abnormalities precede the onset of psychosis and may represent a trait marker. These cognitive alterations may arise from functional disconnectivity, as no significant brain damage has been found. In this review we aim to revise A.R. Luria's systematic approach used in the neuropsychological evaluation of cognitive functions, which was primarily applied in patients with neurological disorders and in the cognitive evaluation in schizophrenia and other related disorders. As proposed by Luria, cognitive processes, associated with higher cortical functions, may represent functional systems that are not localized in narrow, circumscribed areas of the brain, but occur among groups of concertedly working brain structures, each of which makes its own particular contribution to the organization of the functional system. Current developments in neuroscience provide evidence of functional connectivity in the brain. Therefore, Luria's approach may serve as a frame of reference for the analysis and interpretation of cognitive functions in general and their abnormalities in schizophrenia in particular. Having said that, modern technology, as well as experimental evidence, may help us to understand the brain better and lead us towards creating a new classification of cognitive functions. In schizophrenia research, multidisciplinary approaches must be utilized to address specific cognitive alterations. The relationships among the components of cognitive functions derived from the functional connectivity of the brain may provide an insight into cognitive machinery.

Prevalence and spectrum of in utero structural brain abnormalities in fetuses with complex congenital heart disease.

PubMed

Brossard-Racine, M; du Plessis, A J; Vezina, G; Robertson, R; Bulas, D; Evangelou, I E; Donofrio, M; Freeman, D; Limperopoulos, C

2014-08-01

Brain injury is a major complication in neonates with complex congenital heart disease. Preliminary evidence suggests that fetuses with congenital heart disease are at greater risk for brain abnormalities. However, the nature and frequency of these brain abnormalities detected by conventional fetal MR imaging has not been examined prospectively. Our primary objective was to determine the prevalence and spectrum of brain abnormalities detected on conventional clinical MR imaging in fetuses with complex congenital heart disease and, second, to compare the congenital heart disease cohort with a control group of fetuses from healthy pregnancies. We prospectively recruited pregnant women with a confirmed fetal congenital heart disease diagnosis and healthy volunteers with normal fetal echocardiogram findings who underwent a fetal MR imaging between 18 and 39 weeks gestational age. A total of 338 fetuses (194 controls; 144 with congenital heart disease) were studied at a mean gestational age of 30.61 ± 4.67 weeks. Brain abnormalities were present in 23% of the congenital heart disease group compared with 1.5% in the control group (P < .001). The most common abnormalities in the congenital heart disease group were mild unilateral ventriculomegaly in 12/33 (36.4%) and increased extra-axial spaces in 10/33 (30.3%). Subgroup analyses comparing the type and frequency of brain abnormalities based on cardiac physiology did not reveal significant associations, suggesting that the brain abnormalities were not limited to those with the most severe congenital heart disease. This is the first large prospective study reporting conventional MR imaging findings in fetuses with congenital heart disease. Our results suggest that brain abnormalities are prevalent but relatively mild antenatally in fetuses with congenital heart disease. The long-term predictive value of these findings awaits further study. © 2014 by American Journal of Neuroradiology.

Amplitude-integrated EEG in newborns with critical congenital heart disease predicts preoperative brain magnetic resonance imaging findings.

PubMed

Mulkey, Sarah B; Yap, Vivien L; Bai, Shasha; Ramakrishnaiah, Raghu H; Glasier, Charles M; Bornemeier, Renee A; Schmitz, Michael L; Bhutta, Adnan T

2015-06-01

The study aims are to evaluate cerebral background patterns using amplitude-integrated electroencephalography in newborns with critical congenital heart disease, determine if amplitude-integrated electroencephalography is predictive of preoperative brain injury, and assess the incidence of preoperative seizures. We hypothesize that amplitude-integrated electroencephalography will show abnormal background patterns in the early preoperative period in infants with congenital heart disease that have preoperative brain injury on magnetic resonance imaging. Twenty-four newborns with congenital heart disease requiring surgery at younger than 30 days of age were prospectively enrolled within the first 3 days of age at a tertiary care pediatric hospital. Infants had amplitude-integrated electroencephalography for 24 hours beginning close to birth and preoperative brain magnetic resonance imaging. The amplitude-integrated electroencephalographies were read to determine if the background pattern was normal, mildly abnormal, or severely abnormal. The presence of seizures and sleep-wake cycling were noted. The preoperative brain magnetic resonance imaging scans were used for brain injury and brain atrophy assessment. Fifteen of 24 infants had abnormal amplitude-integrated electroencephalography at 0.71 (0-2) (mean [range]) days of age. In five infants, the background pattern was severely abnormal. (burst suppression and/or continuous low voltage). Of the 15 infants with abnormal amplitude-integrated electroencephalography, 9 (60%) had brain injury. One infant with brain injury had a seizure on amplitude-integrated electroencephalography. A severely abnormal background pattern on amplitude-integrated electroencephalography was associated with brain atrophy (P = 0.03) and absent sleep-wake cycling (P = 0.022). Background cerebral activity is abnormal on amplitude-integrated electroencephalography following birth in newborns with congenital heart disease who have findings of brain injury and/or brain atrophy on preoperative brain magnetic resonance imaging. Copyright © 2015 Elsevier Inc. All rights reserved.

Age and sex effects levels of choline compounds in the anterior cingulate cortex of adolescent methamphetamine users.

PubMed

Cloak, Christine C; Alicata, Daniel; Chang, Linda; Andrews-Shigaki, Brian; Ernst, Thomas

2011-12-15

Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug's impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13-23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show age-appropriate levels of ACC CHO. The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

Age and sex effects levels of choline compounds in the anterior cingulate cortex of adolescent methamphetamine users

PubMed Central

Cloak, Christine C.; Alicata, Daniel; Chang, Linda; Andrews-Shigaki, Brian; Ernst, Thomas

2011-01-01

Background Methamphetamine can be neurotoxic to the adult brain; however, many individuals first use methamphetamine during adolescence, and the drug’s impact on this period of brain development is unknown. Therefore, we evaluated young methamphetamine users for possible abnormalities in brain metabolite concentrations. Methods Anterior cingulate cortex (ACC), frontal white matter (FWM), basal ganglia, and thalamus were studied with localized proton magnetic resonance spectroscopy in 54 periadolescent (ages 13–23 years) methamphetamine users and 53 comparison subjects. The concentrations of major brain metabolites and their associations with age, sex and cognition were assessed. Results FWM total-creatine correlated with age in methamphetamine-using males and comparison females, but not comparison males or methamphetamine-using females, leading to a drug by sex by age interaction (p=0.003) and ACC choline-containing compounds (CHO) correlated with age only in comparison males leading to a drug by sex by age interaction (p=0.03). Higher ACC CHO was associated with faster performance on the Stroop Interference task in the control males. Male methamphetamine users had slowest performance on the Stroop Interference task and did not show showed age-appropriate levels of ACC CHO. Conclusions The altered age-appropriate levels of ACC CHO and poorer executive function in male methamphetamine users suggest methamphetamine abuse may interfere with brain maturation. These periadolescents did not have the abnormal neuronal markers previously reported in adult methamphetamine users, suggesting that neuronal abnormalities may be the result of long-term use or interference in normal cortical maturation, emphasizing the need for early intervention for young methamphetamine users. PMID:21775074

More randomized and resilient in the topological properties of functional brain networks in patients with major depressive disorder.

PubMed

Li, Huaizhou; Zhou, Haiyan; Yang, Yang; Wang, Haiyuan; Zhong, Ning

2017-10-01

Previous studies have reported the enhanced randomization of functional brain networks in patients with major depressive disorder (MDD). However, little is known about the changes of key nodal attributes for randomization, the resilience of network, and the clinical significance of the alterations. In this study, we collected the resting-state functional MRI data from 19 MDD patients and 19 healthy control (HC) individuals. Graph theory analysis showed that decreases were found in the small-worldness, clustering coefficient, local efficiency, and characteristic path length (i.e., increase of global efficiency) in the network of MDD group compared with HC group, which was consistent with previous findings and suggested the development toward randomization in the brain network in MDD. In addition, the greater resilience under the targeted attacks was also found in the network of patients with MDD. Furthermore, the abnormal nodal properties were found, including clustering coefficients and nodal efficiencies in the left orbital superior frontal gyrus, bilateral insula, left amygdala, right supramarginal gyrus, left putamen, left posterior cingulate cortex, left angular gyrus. Meanwhile, the correlation analysis showed that most of these abnormal areas were associated with the clinical status. The observed increased randomization and resilience in MDD might be related to the abnormal hub nodes in the brain networks, which were attacked by the disease pathology. Our findings provide new evidence to indicate that the weakening of specialized regions and the enhancement of whole brain integrity could be the potential endophenotype of the depressive pathology. Copyright © 2017 Elsevier Ltd. All rights reserved.

MR Anatomy of Deep Brain Nuclei with Special Reference to Specific Diseases and Deep Brain Stimulation Localization

PubMed Central

Telford, Ryan; Vattoth, Surjith

2014-01-01

Summary Diseases affecting the basal ganglia and deep brain structures vary widely in etiology and include metabolic, infectious, ischemic, and neurodegenerative conditions. Some neurologic diseases, such as Wernicke encephalopathy or pseudohypoparathyroidism, require specific treatments, which if unrecognized could lead to further complications. Other pathologies, such as hypertrophic olivary degeneration, if not properly diagnosed may be mistaken for a primary medullary neoplasm and create unnecessary concern. The deep brain structures are complex and can be difficult to distinguish on routine imaging. It is imperative that radiologists first understand the intrinsic anatomic relationships between the different basal ganglia nuclei and deep brain structures with magnetic resonance (MR) imaging. It is important to understand the "normal" MR signal characteristics, locations, and appearances of these structures. This is essential to recognizing diseases affecting the basal ganglia and deep brain structures, especially since most of these diseases result in symmetrical, and therefore less noticeable, abnormalities. It is also crucial that neurosurgeons correctly identify the deep brain nuclei presurgically for positioning deep brain stimulator leads, the most important being the subthalamic nucleus for Parkinson syndromes and the thalamic ventral intermediate nucleus for essential tremor. Radiologists will be able to better assist clinicians in diagnosis and treatment once they are able to accurately localize specific deep brain structures. PMID:24571832

The influence of brain abnormalities on psychosocial development, criminal history and paraphilias in sexual murderers.

PubMed

Briken, Peer; Habermann, Niels; Berner, Wolfgang; Hill, Andreas

2005-09-01

The aim of this study was to investigate the number and type of brain abnormalities and their influence on psychosocial development, criminal history and paraphilias in sexual murderers. We analyzed psychiatric court reports of 166 sexual murderers and compared a group with notable signs of brain abnormalities (N = 50) with those without any signs (N = 116). Sexual murderers with brain abnormalities suffered more from early behavior problems. They were less likely to cohabitate with the victim at the time of the homicide and had more victims at the age of six years or younger. Psychiatric diagnoses revealed a higher total number of paraphilias: Transvestic fetishism and paraphilias not otherwise specified were more frequent in offenders with brain abnormalities. A binary logistic regression identified five predictors that accounted for 46.8% of the variance explaining the presence of brain abnormalities. Our results suggest the importance of a comprehensive neurological and psychological examination of this special offender group.

Detection and mapping of delays in early cortical folding derived from in utero MRI

NASA Astrophysics Data System (ADS)

Habas, Piotr A.; Rajagopalan, Vidya; Scott, Julia A.; Kim, Kio; Roosta, Ahmad; Rousseau, Francois; Barkovich, A. James; Glenn, Orit A.; Studholme, Colin

2011-03-01

Understanding human brain development in utero and detecting cortical abnormalities related to specific clinical conditions is an important area of research. In this paper, we describe and evaluate methodology for detection and mapping of delays in early cortical folding from population-based studies of fetal brain anatomies imaged in utero. We use a general linear modeling framework to describe spatiotemporal changes in curvature of the developing brain and explore the ability to detect and localize delays in cortical folding in the presence of uncertainty in estimation of the fetal age. We apply permutation testing to examine which regions of the brain surface provide the most statistical power to detect a given folding delay at a given developmental stage. The presented methodology is evaluated using MR scans of fetuses with normal brain development and gestational ages ranging from 20.57 to 27.86 weeks. This period is critical in early cortical folding and the formation of the primary and secondary sulci. Finally, we demonstrate a clinical application of the framework for detection and localization of folding delays in fetuses with isolated mild ventriculomegaly.

Increased resting-state brain entropy in Alzheimer's disease.

PubMed

Xue, Shao-Wei; Guo, Yonghu

2018-03-07

Entropy analysis of resting-state functional MRI (R-fMRI) is a novel approach to characterize brain temporal dynamics and facilitates the identification of abnormal brain activity caused by several disease conditions. However, Alzheimer's disease (AD)-related brain entropy mapping based on R-fMRI has not been assessed. Here, we measured the sample entropy and voxel-wise connectivity of the network degree centrality (DC) of the intrinsic brain activity acquired by R-fMRI in 26 patients with AD and 26 healthy controls. Compared with the controls, AD patients showed increased entropy in the middle temporal gyrus and the precentral gyrus and also showed decreased DC in the precuneus. Moreover, the magnitude of the negative correlation between local brain activity (entropy) and network connectivity (DC) was increased in AD patients in comparison with healthy controls. These findings provide new evidence on AD-related brain entropy alterations.

Behavioral Analysis of Genetically Modified Mice Indicates Essential Roles of Neurosteroidal Estrogen

PubMed Central

Honda, Shin-Ichiro; Wakatsuki, Toru; Harada, Nobuhiro

2011-01-01

Aromatase in the mouse brain is expressed only in the nerve cells of specific brain regions with a transient peak during the neonatal period when sexual behaviors become organized. The aromatase-knockout (ArKO) mouse, generated to shed light on the physiological functions of estrogen in the brain, exhibited various abnormal behaviors, concomitant with undetectable estrogen and increased androgen in the blood. To further elucidate the effects of neurosteroidal estrogens on behavioral phenotypes, we first prepared an brain-specific aromatase transgenic (bsArTG) mouse by introduction of a human aromatase transgene controlled under a −6.5 kb upstream region of the brain-specific promoter of the mouse aromatase gene into fertilized mouse eggs, because the −6.5 kb promoter region was previously shown to contain the minimal essential element responsible for brain-specific spatiotemporal expression. Then, an ArKO mouse expressing the human aromatase only in the brain was generated by crossing the bsArTG mouse with the ArKO mouse. The resulting mice (ArKO/bsArTG mice) nearly recovered from abnormal sexual, aggressive, and locomotive (exploratory) behaviors, in spite of having almost the same serum levels of estrogen and androgen as the adult ArKO mouse. These results suggest that estrogens locally synthesized in the specific neurons of the perinatal mouse brain directly act on the neurons and play crucial roles in the organization of neuronal networks participating in the control of sexual, aggressive, and locomotive (exploratory) behaviors. PMID:22654807

Sexually dimorphic white matter geometry abnormalities in adolescent onset schizophrenia.

PubMed

Savadjiev, P; Whitford, T J; Hough, M E; Clemm von Hohenberg, C; Bouix, S; Westin, C-F; Shenton, M E; Crow, T J; James, A C; Kubicki, M

2014-05-01

The normal human brain is characterized by a pattern of gross anatomical asymmetry. This pattern, known as the "torque", is associated with a sexual dimorphism: The male brain tends to be more asymmetric than that of the female. This fact, along with well-known sex differences in brain development (faster in females) and onset of psychosis (earlier with worse outcome in males), has led to the theory that schizophrenia is a disorder in which sex-dependent abnormalities in the development of brain torque, the correlate of the capacity for language, cause alterations in interhemispheric connectivity, which are causally related to psychosis (Crow TJ, Paez P, Chance SE. 2007. Callosal misconnectivity and the sex difference in psychosis. Int Rev Psychiatry. 19(4):449-457.). To provide evidence toward this theory, we analyze the geometry of interhemispheric white matter connections in adolescent-onset schizophrenia, with a particular focus on sex, using a recently introduced framework for white matter geometry computation in diffusion tensor imaging data (Savadjiev P, Kindlmann GL, Bouix S, Shenton ME, Westin CF. 2010. Local white geometry from diffusion tensor gradients. Neuroimage. 49(4):3175-3186.). Our results reveal a pattern of sex-dependent white matter geometry abnormalities that conform to the predictions of Crow's torque theory and correlate with the severity of patients' symptoms. To the best of our knowledge, this is the first study to associate geometrical differences in white matter connectivity with torque in schizophrenia.

Changes in functional connectivity of the brain associated with a history of sport concussion: A preliminary investigation.

PubMed

Churchill, Nathan; Hutchison, Michael G; Leung, General; Graham, Simon; Schweizer, Tom A

2017-01-01

There is evidence of long-term clinical consequences associated with a history of sport concussion. However, there remains limited information about the underlying changes in brain function. The goal of this study was to identify brain regions where abnormal resting-state function is associated with chronic concussion, for athletes without persistent symptoms. Functional Magnetic Resonance Imaging (fMRI) was performed on a group of athletes with prior concussion (n = 22) and a group without documented injury (n = 21). Multivariate predictive modelling was used to localize reliable changes in brain connectivity that are associated with a history of concussion and with clinical factors, including number of prior concussions and recovery time from last injury. No significant differences were found between athletes with and without a history of concussion, but functional connectivity was significantly associated with clinical history. The number of prior concussions was associated with most extensive connectivity changes, particularly for elements of the visual attention network and cerebellum. The findings of this preliminary study indicate that functional brain abnormalities associated with chronic concussion may be significantly dependent on clinical history. In addition, elements of the visual and cerebellar systems may be most sensitive to the long-term effects of sport concussion.

Histone Deacetylase 3 Is Necessary for Proper Brain Development*

PubMed Central

Norwood, Jordan; Franklin, Jade M.; Sharma, Dharmendra; D'Mello, Santosh R.

2014-01-01

The functional role of histone deacetylase 3 (HDAC3) in the developing brain has yet to be elucidated. We show that mice lacking HDAC3 in neurons and glia of the central nervous system, Nes-Cre/HDAC3 conditional KO mice, show major abnormalities in the cytoarchitecture of the neocortex and cerebellum and die within 24 h of birth. Later-born neurons do not localize properly in the cortex. A similar mislocalization is observed with cerebellar Purkinje neurons. Although the proportion of astrocytes is higher than normal, the numbers of oligodendrocytes are reduced. In contrast, conditional knockout of HDAC3 in neurons of the forebrain and certain other brain regions, using Thy1-Cre and calcium/calmodulin dependent protein kinase II α-Cre for ablation, produces no overt abnormalities in the organization of cells within the cortex or of cerebellar Purkinje neurons at birth. However, both lines of conditional knockout mice suffer from progressive hind limb paralysis and ataxia and die around 6 weeks after birth. The mice display an increase in overall numbers of cells, higher numbers of astrocytes, and Purkinje neuron degeneration. Taken together, our results demonstrate that HDAC3 plays an essential role in regulating brain development, with effects on both neurons and glia in different brain regions. PMID:25339172

Brain and bone abnormalities of thanatophoric dwarfism.

PubMed

Miller, Elka; Blaser, Susan; Shannon, Patrick; Widjaja, Elysa

2009-01-01

The purpose of this article is to present the imaging findings of skeletal and brain abnormalities in thanatophoric dwarfism, a lethal form of dysplastic dwarfism. The bony abnormalities associated with thanatophoric dwarfism include marked shortening of the tubular bones and ribs. Abnormal temporal lobe development is a common associated feature and can be visualized as early as the second trimester. It is important to assess the brains of fetuses with suspected thanatophoric dwarfism because the presence of associated brain malformations can assist in the antenatal diagnosis of thanatophoric dwarfism.

Regional brain glucose metabolism in patients with brain tumors before and after radiotherapy

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, G.J.; Volkow, N.D.; Lau, Y.H.

1994-05-01

This study was performed to measure regional glucose metabolism in nonaffected brain regions of patients with primary or metastatic brain tumors. Seven female and four male patients (mean age 51.5{plus_minus}14.0 years old) were compared with eleven age and sex matched normal subjects. None of the patients had hydrocephalus and/or increased intracranial pressure. Brain glucose metabolism was measured using FDG-PET scan. Five of the patients were reevaluated one week after receiving radiation treatment (RT) to the brain. Patients were on Decadron and/or Dilantin at the time of both scan. PET images were analyzed with a template of 115 nonoverlapping regions ofmore » interest and then grouped into eight gray matter regions on each hemisphere. Brain regions with tumors and edema shown in MR imaging were excluded. Z scores were used to compare individual patients` regional values with those of normal subjects. The number of regional values with Z scores of less than - 3.0 were considered abnormal and were quantified. The mean global glucose metabolic rate (mean of all regions) in nonaffected brain regions of patients was significantly lower than that of normal controls (32.1{plus_minus}9.0 versus 44.8{plus_minus}6.3 {mu}mol/100g/min, p<0.001). Analyses of individual subjects revealed that none of the controls and 8 of the 11 patients had at least one abnormal region. In these 8 patients the regions which were abnormal were most frequently localized in right (n=5) and left occipital (n=6) and right orbital frontal cortex (n=7) whereas the basal ganglia was not affected. Five of the patients who had repeated scans following RT showed decrements in tumor metabolism (41{plus_minus}20.5%) and a significant increase in whole brain metabolism (8.6{plus_minus}5.3%, p<0.001). The improvement in whole brain metabolism after RT suggests that the brain metabolic decrements in the patients were related to the presence of tumoral tissue and not just a medication effect.« less

Abnormal white matter integrity in chronic users of codeine-containing cough syrups: a tract-based spatial statistics study.

PubMed

Qiu, Y-W; Su, H-H; Lv, X-F; Jiang, G-H

2015-01-01

Codeine-containing cough syrups have become one of the most popular drugs of abuse in young people in the world. Chronic codeine-containing cough syrup abuse is related to impairments in a broad range of cognitive functions. However, the potential brain white matter impairment caused by chronic codeine-containing cough syrup abuse has not been reported previously. Our aim was to investigate abnormalities in the microstructure of brain white matter in chronic users of codeine-containing syrups and to determine whether these WM abnormalities are related to the duration of the use these syrups and clinical impulsivity. Thirty chronic codeine-containing syrup users and 30 matched controls were evaluated. Diffusion tensor imaging was performed by using a single-shot spin-echo-planar sequence. Whole-brain voxelwise analysis of fractional anisotropy was performed by using tract-based spatial statistics to localize abnormal WM regions. The Barratt Impulsiveness Scale 11 was surveyed to assess participants' impulsivity. Volume-of-interest analysis was used to detect changes of diffusivity indices in regions with fractional anisotropy abnormalities. Abnormal fractional anisotropy was extracted and correlated with clinical impulsivity and the duration of codeine-containing syrup use. Chronic codeine-containing syrup users had significantly lower fractional anisotropy in the inferior fronto-occipital fasciculus of the bilateral temporo-occipital regions, right frontal region, and the right corona radiata WM than controls. There were significant negative correlations among fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the right superior corona radiata WM and Barratt Impulsiveness Scale total scores, and between the right frontal region of the inferior fronto-occipital fasciculus and nonplan impulsivity scores in chronic codeine-containing syrup users. There was also a significant negative correlation between fractional anisotropy values of the right frontal region of the inferior fronto-occipital fasciculus and the duration of codeine-containing syrup use in chronic users. Chronic codeine-containing syrup abuse may be associated with disruptions in brain WM integrity. These WM microstructural deficits may be linked to higher impulsivity in chronic codeine-containing syrup users. © 2015 by American Journal of Neuroradiology.

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI

PubMed Central

Xu, Tingting; Cullen, Kathryn R.; Mueller, Bryon; Schreiner, Mindy W.; Lim, Kelvin O.; Schulz, S. Charles; Parhi, Keshab K.

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03–0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03–0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works. PMID:26977400

Network analysis of functional brain connectivity in borderline personality disorder using resting-state fMRI.

PubMed

Xu, Tingting; Cullen, Kathryn R; Mueller, Bryon; Schreiner, Mindy W; Lim, Kelvin O; Schulz, S Charles; Parhi, Keshab K

2016-01-01

Borderline personality disorder (BPD) is associated with symptoms such as affect dysregulation, impaired sense of self, and self-harm behaviors. Neuroimaging research on BPD has revealed structural and functional abnormalities in specific brain regions and connections. However, little is known about the topological organizations of brain networks in BPD. We collected resting-state functional magnetic resonance imaging (fMRI) data from 20 patients with BPD and 10 healthy controls, and constructed frequency-specific functional brain networks by correlating wavelet-filtered fMRI signals from 82 cortical and subcortical regions. We employed graph-theory based complex network analysis to investigate the topological properties of the brain networks, and employed network-based statistic to identify functional dysconnections in patients. In the 0.03-0.06 Hz frequency band, compared to controls, patients with BPD showed significantly larger measures of global network topology, including the size of largest connected graph component, clustering coefficient, small-worldness, and local efficiency, indicating increased local cliquishness of the functional brain network. Compared to controls, patients showed lower nodal centrality at several hub nodes but greater centrality at several non-hub nodes in the network. Furthermore, an interconnected subnetwork in 0.03-0.06 Hz frequency band was identified that showed significantly lower connectivity in patients. The links in the subnetwork were mainly long-distance connections between regions located at different lobes; and the mean connectivity of this subnetwork was negatively correlated with the increased global topology measures. Lastly, the key network measures showed high correlations with several clinical symptom scores, and classified BPD patients against healthy controls with high accuracy based on linear discriminant analysis. The abnormal topological properties and connectivity found in this study may add new knowledge to the current understanding of functional brain networks in BPD. However, due to limitation of small sample sizes, the results of the current study should be viewed as exploratory and need to be validated on large samples in future works.

A voxel-based investigation of brain structure in male adolescents with autistic spectrum disorder.

PubMed

Waiter, Gordon D; Williams, Justin H G; Murray, Alison D; Gilchrist, Anne; Perrett, David I; Whiten, Andrew

2004-06-01

Autistic spectrum disorder (ASD) has been associated with abnormal neuroanatomy in many imaging and neuropathological studies. Both global brain volume differences and differences in the size of specific neural structures have been reported. Here, we report a voxel-based morphometric whole brain analysis, using a group specific template, on 16 individuals of normal intelligence with autistic spectrum disorder (ASD), and a group of 16 age-, sex- and IQ-matched controls. Total grey matter volume was increased in the ASD group relative to the control group, with local volume increases in the right fusiform gyrus, the right temporo-occipital region and the left frontal pole extending to the medial frontal cortex. A local decrease in grey matter volume was found in the right thalamus. A decrease in global white matter volume in the ASD group did not reach significance. We found the increase in grey matter volume in ASD subjects was greatest in those areas recognised for their role in social cognition, particularly face recognition (right fusiform gyrus), mental state attribution: 'theory of mind' (anterior cingulate and superior temporal sulcus) and perception of eye gaze (superior temporal gyrus). The picture as a whole may reflect an abnormally functioning social cognitive neural network. We suggest that increased grey matter volume may play a pivotal role in the aetiology of the autistic syndrome.

Radiation-induced brain structural and functional abnormalities in presymptomatic phase and outcome prediction.

PubMed

Ding, Zhongxiang; Zhang, Han; Lv, Xiao-Fei; Xie, Fei; Liu, Lizhi; Qiu, Shijun; Li, Li; Shen, Dinggang

2018-01-01

Radiation therapy, a major method of treatment for brain cancer, may cause severe brain injuries after many years. We used a rare and unique cohort of nasopharyngeal carcinoma patients with normal-appearing brains to study possible early irradiation injury in its presymptomatic phase before severe, irreversible necrosis happens. The aim is to detect any structural or functional imaging biomarker that is sensitive to early irradiation injury, and to understand the recovery and progression of irradiation injury that can shed light on outcome prediction for early clinical intervention. We found an acute increase in local brain activity that is followed by extensive reductions in such activity in the temporal lobe and significant loss of functional connectivity in a distributed, large-scale, high-level cognitive function-related brain network. Intriguingly, these radiosensitive functional alterations were found to be fully or partially recoverable. In contrast, progressive late disruptions to the integrity of the related far-end white matter structure began to be significant after one year. Importantly, early increased local brain functional activity was predictive of severe later temporal lobe necrosis. Based on these findings, we proposed a dynamic, multifactorial model for radiation injury and another preventive model for timely clinical intervention. Hum Brain Mapp 39:407-427, 2018. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

Prevention of Blast-Related Injuries

DTIC Science & Technology

2017-09-01

allow early screening and assessment of brain abnormality in soldiers to enable timely therapeutic intervention. The current study reports on the...use of qEEG in blast-induced brain injury using a swine model. The purposes are to determine if qEEG can detect brain activity abnormalities early...brain functional abnormalities and deficits in absence of any clinical mTBI symptoms. Methods such as EEG-wavelet entropy measures [36] and Shannon

Preliminary Evidence of White Matter Abnormality in the Uncinate Fasciculus in Generalized Social Anxiety Disorder

PubMed Central

Phan, K. Luan; Orlichenko, Anton; Boyd, Erin; Angstadt, Mike; Coccaro, Emil F.; Liberzon, Israel; Arfanakis, Konstantinos

2009-01-01

Background Individuals with generalized social anxiety disorder (GSAD) exhibit exaggerated amygdala reactivity to aversive social stimuli. These findings could be explained by microstructural abnormalities in white matter (WM) tracts that connect the amygdala and prefrontal cortex, which is known to modulate the amygdala’s response to threat. The goal of this study was to investigate brain frontal WM abnormalities by using diffusion tensor imaging (DTI) in patients with social anxiety disorder. Method A Turboprop DTI sequence was used to acquire diffusion tensor images in thirty patients with GSAD and thirty matched healthy controls. Fractional anisotropy, an index of axonal organization, within WM was quantified in individual subjects and an automated voxel-based, whole-brain method was used to analyze group differences. Results Compared to healthy controls, patients had significantly lower fractional anisotropy localized to the right uncinate fasciculus WM near the orbitofrontal cortex. There were no areas of higher fractional anisotropy in patients than controls. Conclusions These findings point to an abnormality in the uncinate fasciculus, the major WM tract connecting the frontal cortex to the amygdala and other limbic temporal regions, in GSAD which could underlie the aberrant amygdala-prefrontal interactions resulting in dysfunctional social threat processing in this illness. PMID:19362707

A Window into the Brain: Advances in Psychiatric fMRI

PubMed Central

Zhan, Xiaoyan

2015-01-01

Functional magnetic resonance imaging (fMRI) plays a key role in modern psychiatric research. It provides a means to assay differences in brain systems that underlie psychiatric illness, treatment response, and properties of brain structure and function that convey risk factor for mental diseases. Here we review recent advances in fMRI methods in general use and progress made in understanding the neural basis of mental illness. Drawing on concepts and findings from psychiatric fMRI, we propose that mental illness may not be associated with abnormalities in specific local regions but rather corresponds to variation in the overall organization of functional communication throughout the brain network. Future research may need to integrate neuroimaging information drawn from different analysis methods and delineate spatial and temporal patterns of brain responses that are specific to certain types of psychiatric disorders. PMID:26413531

Granger Causality Relationships between Local Field Potentials in an Animal Model of Temporal Lobe Epilepsy

PubMed Central

Cadotte, Alex J.; DeMarse, Thomas B.; Mareci, Thomas H.; Parekh, Mansi; Talathi, Sachin S.; Hwang, Dong-Uk; Ditto, William L.; Ding, Mingzhou; Carney, Paul R.

2010-01-01

An understanding of the in vivo spatial emergence of abnormal brain activity during spontaneous seizure onset is critical to future early seizure detection and closed-loop seizure prevention therapies. In this study, we use Granger causality (GC) to determine the strength and direction of relationships between local field potentials (LFPs) recorded from bilateral microelectrode arrays in an intermittent spontaneous seizure model of chronic temporal lobe epilepsy before, during, and after Racine grade partial onset generalized seizures. Our results indicate distinct patterns of directional GC relationships within the hippocampus, specifically from the CA1 subfield to the dentate gryus, prior to and during seizure onset. Our results suggest sequential and hierarchical temporal relationships between the CA1 and dentate gyrus within and across hippocampal hemispheres during seizure. Additionally, our analysis suggests a reversal in the direction of GC relationships during seizure, from an abnormal pattern to more anatomically expected pattern. This reversal correlates well with the observed behavioral transition from tonic to clonic seizure in time-locked video. These findings highlight the utility of GC to reveal dynamic directional temporal relationships between multichannel LFP recordings from multiple brain regions during unprovoked spontaneous seizures. PMID:20304005

Granger causality relationships between local field potentials in an animal model of temporal lobe epilepsy.

PubMed

Cadotte, Alex J; DeMarse, Thomas B; Mareci, Thomas H; Parekh, Mansi B; Talathi, Sachin S; Hwang, Dong-Uk; Ditto, William L; Ding, Mingzhou; Carney, Paul R

2010-05-30

An understanding of the in vivo spatial emergence of abnormal brain activity during spontaneous seizure onset is critical to future early seizure detection and closed-loop seizure prevention therapies. In this study, we use Granger causality (GC) to determine the strength and direction of relationships between local field potentials (LFPs) recorded from bilateral microelectrode arrays in an intermittent spontaneous seizure model of chronic temporal lobe epilepsy before, during, and after Racine grade partial onset generalized seizures. Our results indicate distinct patterns of directional GC relationships within the hippocampus, specifically from the CA1 subfield to the dentate gyrus, prior to and during seizure onset. Our results suggest sequential and hierarchical temporal relationships between the CA1 and dentate gyrus within and across hippocampal hemispheres during seizure. Additionally, our analysis suggests a reversal in the direction of GC relationships during seizure, from an abnormal pattern to more anatomically expected pattern. This reversal correlates well with the observed behavioral transition from tonic to clonic seizure in time-locked video. These findings highlight the utility of GC to reveal dynamic directional temporal relationships between multichannel LFP recordings from multiple brain regions during unprovoked spontaneous seizures. (c) 2010 Elsevier B.V. All rights reserved.

White matter structural network abnormalities underlie executive dysfunction in amyotrophic lateral sclerosis.

PubMed

Dimond, Dennis; Ishaque, Abdullah; Chenji, Sneha; Mah, Dennell; Chen, Zhang; Seres, Peter; Beaulieu, Christian; Kalra, Sanjay

2017-03-01

Research in amyotrophic lateral sclerosis (ALS) suggests that executive dysfunction, a prevalent cognitive feature of the disease, is associated with abnormal structural connectivity and white matter integrity. In this exploratory study, we investigated the white matter constructs of executive dysfunction, and attempted to detect structural abnormalities specific to cognitively impaired ALS patients. Eighteen ALS patients and 22 age and education matched healthy controls underwent magnetic resonance imaging on a 4.7 Tesla scanner and completed neuropsychometric testing. ALS patients were categorized into ALS cognitively impaired (ALSci, n = 9) and ALS cognitively competent (ALScc, n = 5) groups. Tract-based spatial statistics and connectomics were used to compare white matter integrity and structural connectivity of ALSci and ALScc patients. Executive function performance was correlated with white matter FA and network metrics within the ALS group. Executive function performance in the ALS group correlated with global and local network properties, as well as FA, in regions throughout the brain, with a high predilection for the frontal lobe. ALSci patients displayed altered local connectivity and structural integrity in these same frontal regions that correlated with executive dysfunction. Our results suggest that executive dysfunction in ALS is related to frontal network disconnectivity, which potentially mediates domain-specific, or generalized cognitive impairment, depending on the degree of global network disruption. Furthermore, reported co-localization of decreased network connectivity and diminished white matter integrity suggests white matter pathology underlies this topological disruption. We conclude that executive dysfunction in ALSci is associated with frontal and global network disconnectivity, underlined by diminished white matter integrity. Hum Brain Mapp 38:1249-1268, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Added Value of Including Entire Brain on Body Imaging With FDG PET/MRI.

PubMed

Franceschi, Ana M; Matthews, Robert; Bangiyev, Lev; Relan, Nand; Chaudhry, Ammar; Franceschi, Dinko

2018-05-24

FDG PET/MRI examination of the body is routinely performed from the skull base to the mid thigh. Many types of brain abnormalities potentially could be detected on PET/MRI if the head was included. The objective of this study was therefore to identify and characterize brain findings incidentally detected on PET/MRI of the body with the head included. We retrospectively identified 269 patients with FDG PET/MRI whole-body scans that included the head. PET/MR images of the brain were reviewed by a nuclear medicine physician and neuroradiologist, first individually and then concurrently. Both PET and MRI findings were identified, including abnormal FDG uptake, standardized uptake value, lesion size, and MRI signal characteristics. For each patient, relevant medical history and prior imaging were reviewed. Of the 269 subjects, 173 were women and 96 were men (mean age, 57.4 years). Only the initial PET/MR image of each patient was reviewed. A total of 37 of the 269 patients (13.8%) had abnormal brain findings noted on the PET/MRI whole-body scan. Sixteen patients (5.9%) had vascular disease, nine patients (3.3%) had posttherapy changes, and two (0.7%) had benign cystic lesions in the brain. Twelve patients (4.5%) had serious nonvascular brain abnormalities, including cerebral metastasis in five patients and pituitary adenomas in two patients. Only nine subjects (3.3%) had a new neurologic or cognitive symptom suggestive of a brain abnormality. Routine body imaging with FDG PET/MRI of the area from the skull base to the mid thigh may miss important brain abnormalities when the head is not included. The additional brain abnormalities identified on whole-body imaging may provide added clinical value to the management of oncology patients.

A foldable electrode array for 3D recording of deep-seated abnormal brain cavities

NASA Astrophysics Data System (ADS)

Kil, Dries; De Vloo, Philippe; Fierens, Guy; Ceyssens, Frederik; Hunyadi, Borbála; Bertrand, Alexander; Nuttin, Bart; Puers, Robert

2018-06-01

Objective. This study describes the design and microfabrication of a foldable thin-film neural implant and investigates its suitability for electrical recording of deep-lying brain cavity walls. Approach. A new type of foldable neural electrode array is presented, which can be inserted through a cannula. The microfabricated electrode is specifically designed for electrical recording of the cavity wall of thalamic lesions resulting from stroke. The proof-of-concept is demonstrated by measurements in rat brain cavities. On implantation, the electrode array unfolds in the brain cavity, contacting the cavity walls and allowing recording at multiple anatomical locations. A three-layer microfabrication process based on UV-lithography and Reactive Ion Etching is described. Electrochemical characterization of the electrode is performed in addition to an in vivo experiment in which the implantation procedure and the unfolding of the electrode are tested and visualized. Main results. Electrochemical characterization validated the suitability of the electrode for in vivo use. CT imaging confirmed the unfolding of the electrode in the brain cavity and analysis of recorded local field potentials showed the ability to record neural signals of biological origin. Significance. The conducted research confirms that it is possible to record neural activity from the inside wall of brain cavities at various anatomical locations after a single implantation procedure. This opens up possibilities towards research of abnormal brain cavities and the clinical conditions associated with them, such as central post-stroke pain.

Brain functional network abnormality extends beyond the sensorimotor network in brachial plexus injury patients.

PubMed

Feng, Jun-Tao; Liu, Han-Qiu; Hua, Xu-Yun; Gu, Yu-Dong; Xu, Jian-Guang; Xu, Wen-Dong

2016-12-01

Brachial plexus injury (BPI) is a type of severe peripheral nerve trauma that leads to central remodeling in the brain, as revealed by functional MRI analysis. However, previously reported remodeling is mostly restricted to sensorimotor areas of the brain. Whether this disturbance in the sensorimotor network leads to larger-scale functional remodeling remains unknown. We sought to explore the higher-level brain functional abnormality pattern of BPI patients from a large-scale network function connectivity dimension in 15 right-handed BPI patients. Resting-state functional MRI data were collected and analyzed using independent component analysis methods. Five components of interest were recognized and compared between patients and healthy subjects. Patients showed significantly altered brain local functional activities in the bilateral fronto-parietal network (FPN), sensorimotor network (SMN), and executive-control network (ECN) compared with healthy subjects. Moreover, functional connectivity between SMN and ECN were significantly less in patients compared with healthy subjects, and connectivity strength between ECN and SMN was negatively correlated with patients' residual function of the affected limb. Functional connectivity between SMN and right FPN were also significantly less than in controls, although connectivity between ECN and default mode network (DMN) was greater than in controls. These data suggested that brain functional disturbance in BPI patients extends beyond the sensorimotor network and cascades serial remodeling in the brain, which significantly correlates with residual hand function of the paralyzed limb. Furthermore, functional remodeling in these higher-level functional networks may lead to cognitive alterations in complex tasks.

Neural conduction abnormality in the brain stem and prevalence of the abnormality in late preterm infants with perinatal problems.

PubMed

Jiang, Ze Dong

2013-08-01

Neurodevelopment in late preterm infants has recently attracted considerable interest. The prevalence of brain stem conduction abnormality remains unknown. We examined maximum length sequence brain stem auditory evoked response in 163 infants, born at 33-36 weeks gestation, who had various perinatal problems. Compared with 49 normal term infants without problems, the late preterm infants showed a significant increase in III-V and I-V interpeak intervals at all 91-910/s clicks, particularly at 455 and 910/s (p < 0.01-0.001). The I-III interval was slightly increased, without statistically significant difference from the controls at any click rates. These results suggest that neural conduction along the, mainly more central or rostral part of, auditory brain stem is abnormal in late preterm infants with perinatal problems. Of the 163 late preterm infant, the number (and percentage rate) of infants with abnormal I-V interval at 91, 227, 455, and 910/s clicks was, respectively, 11 (6.5%), 17 (10.2%), 37 (22.3%), and 31 (18.7%). The number (and percentage rate) of infants with abnormal III-V interval at these rates was, respectively, 10 (6.0%), 17 (10.2%), 28 (16.9), and 36 (21.2%). Apparently, the abnormal rates were much higher at 455 and 910/s clicks than at lower rates 91 and 227/s. In total, 42 (25.8%) infants showed abnormal I-V and/or III-V intervals. Conduction in, mainly in the more central part, the brain stem is abnormal in late preterm infants with perinatal problems. The abnormality is more detectable at high- than at low-rate sensory stimulation. A quarter of late preterm infants with perinatal problems have brain stem conduction abnormality.

Altered intrinsic functional brain architecture in female patients with bulimia nervosa

PubMed Central

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun’Ai; Correll, Christoph U.; Mitchell, Philip B.; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-01-01

Background Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. Methods We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. Results We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. Limitations We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Conclusion Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa. PMID:28949286

Altered intrinsic functional brain architecture in female patients with bulimia nervosa.

PubMed

Wang, Li; Kong, Qing-Mei; Li, Ke; Li, Xue-Ni; Zeng, Ya-Wei; Chen, Chao; Qian, Ying; Feng, Shi-Jie; Li, Ji-Tao; Su, Yun'Ai; Correll, Christoph U; Mitchell, Philip B; Yan, Chao-Gan; Zhang, Da-Rong; Si, Tian-Mei

2017-11-01

Bulimia nervosa is a severe psychiatric syndrome with uncertain pathogenesis. Neural systems involved in sensorimotor and visual processing, reward and impulsive control may contribute to the binge eating and purging behaviours characterizing bulimia nervosa. However, little is known about the alterations of functional organization of whole brain networks in individuals with this disorder. We used resting-state functional MRI and graph theory to characterize functional brain networks of unmedicated women with bulimia nervosa and healthy women. We included 44 unmedicated women with bulimia nervosa and 44 healthy women in our analyses. Women with bulimia nervosa showed increased clustering coefficient and path length compared with control women. The nodal strength in patients with the disorder was higher in the sensorimotor and visual regions as well as the precuneus, but lower in several subcortical regions, such as the hippocampus, parahippocampal gyrus and orbitofrontal cortex. Patients also showed hyperconnectivity primarily involving sensorimotor and unimodal visual association regions, but hypoconnectivity involving subcortical (striatum, thalamus), limbic (amygdala, hippocampus) and paralimbic (orbitofrontal cortex, parahippocampal gyrus) regions. The topological aberrations correlated significantly with scores of bulimia and drive for thinness and with body mass index. We reruited patients with only acute bulimia nervosa, so it is unclear whether the topological abnormalities comprise vulnerability markers for the disorder developing or the changes associated with illness state. Our findings show altered intrinsic functional brain architecture, specifically abnormal global and local efficiency, as well as nodal- and network-level connectivity across sensorimotor, visual, subcortical and limbic systems in women with bulimia nervosa, suggesting that it is a disorder of dysfunctional integration among large-scale distributed brain regions. These abnormalities contribute to more comprehensive understanding of the neural mechanism underlying pathological eating and body perception in women with bulimia nervosa.

The impact of ADHD persistence, recent cannabis use, and age of regular cannabis use onset on subcortical volume and cortical thickness in young adults.

PubMed

Lisdahl, Krista M; Tamm, Leanne; Epstein, Jeffery N; Jernigan, Terry; Molina, Brooke S G; Hinshaw, Stephen P; Swanson, James M; Newman, Erik; Kelly, Clare; Bjork, James M

2016-04-01

Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

The Impact of ADHD Persistence, Recent Cannabis Use, and Age of Regular Cannabis Use Onset on Subcortical Volume and Cortical Thickness in Young Adults

PubMed Central

Lisdahl, Krista M.; Tamm, Leanne; Epstein, Jeffery N.; Jernigan, Terry; Molina, Brooke S.G.; Hinshaw, Stephen P.; Swanson, James M.; Newman, Erik; Kelly, Clare; Bjork, James M.

2017-01-01

Background Both Attention Deficit Hyperactivity Disorder (ADHD) and chronic cannabis (CAN) use have been associated with brain structural abnormalities, although little is known about the effects of both in young adults. Methods Participants included: those with a childhood diagnosis of ADHD who were CAN users (ADHD_CAN; n=37) and non-users (NU) (ADHD_NU; n=44) and a local normative comparison group (LNCG) who did (LNCG_CAN; n=18) and did not (LNCG_NU; n=21) use CAN regularly. Multiple regressions and MANCOVAs were used to examine the independent and interactive effects of a childhood ADHD diagnosis and CAN group status and age of onset (CUO) on subcortical volumes and cortical thickness. Results After controlling for age, gender, total brain volume, nicotine use, and past-year binge drinking, childhood ADHD diagnosis did not predict brain structure; however, persistence of ADHD was associated with smaller left precentral/postcentral cortical thickness. Compared to all non-users, CAN users had decreased cortical thickness in right hemisphere superior frontal sulcus, anterior cingulate, and isthmus of cingulate gyrus regions and left hemisphere superior frontal sulcus and precentral gyrus regions. Early cannabis use age of onset (CUO) in those with ADHD predicted greater right hemisphere superior frontal and postcentral cortical thickness. Discussion Young adults with persistent ADHD demonstrated brain structure abnormalities in regions underlying motor control, working memory and inhibitory control. Further, CAN use was linked with abnormal brain structure in regions with high concentrations of cannabinoid receptors. Additional large-scale longitudinal studies are needed to clarify how substance use impacts neurodevelopment in youth with and without ADHD. PMID:26897585

Continuum of neurobehaviour and its associations with brain MRI in infants born preterm

PubMed Central

Eeles, Abbey L; Walsh, Jennifer M; Olsen, Joy E; Cuzzilla, Rocco; Thompson, Deanne K; Anderson, Peter J; Doyle, Lex W; Cheong, Jeanie L Y; Spittle, Alicia J

2017-01-01

Background Infants born very preterm (VPT) and moderate-to-late preterm (MLPT) are at increased risk of long-term neurodevelopmental deficits, but how these deficits relate to early neurobehaviour in MLPT children is unclear. The aims of this study were to compare the neurobehavioural performance of infants born across three different gestational age groups: preterm <30 weeks’ gestational age (PT<30); MLPT (32–36 weeks’ gestational age) and term age (≥37 weeks’ gestational age), and explore the relationships between MRI brain abnormalities and neurobehaviour at term-equivalent age. Methods Neurobehaviour was assessed at term-equivalent age in 149 PT<30, 200 MLPT and 200 term-born infants using the Neonatal Intensive Care UnitNetwork Neurobehavioral Scale (NNNS), the Hammersmith Neonatal Neurological Examination (HNNE) and Prechtl’s Qualitative Assessment of General Movements (GMA). A subset of 110 PT<30 and 198 MLPT infants had concurrent brain MRI. Results Proportions with abnormal neurobehaviour on the NNNS and the HNNE, and abnormal GMA all increased with decreasing gestational age. Higher brain MRI abnormality scores in some regions were associated with suboptimal neurobehaviour on the NNNS and HNNE. The relationships between brain MRI abnormality scores and suboptimal neurobehaviour were similar in both PT<30 and MLPT infants. The relationship between brain MRI abnormality scores and abnormal GMA was stronger in PT<30 infants. Conclusions There was a continuum of neurobehaviour across gestational ages. The relationships between brain abnormality scores and suboptimal neurobehaviour provide evidence that neurobehavioural assessments offer insight into the integrity of the developing brain, and may be useful in earlier identification of the highest-risk infants. PMID:29637152

Imaging functional and structural brain connectomics in attention-deficit/hyperactivity disorder.

PubMed

Cao, Miao; Shu, Ni; Cao, Qingjiu; Wang, Yufeng; He, Yong

2014-12-01

Attention-deficit/hyperactivity disorder (ADHD) is one of the most common neurodevelopment disorders in childhood. Clinically, the core symptoms of this disorder include inattention, hyperactivity, and impulsivity. Previous studies have documented that these behavior deficits in ADHD children are associated with not only regional brain abnormalities but also changes in functional and structural connectivity among regions. In the past several years, our understanding of how ADHD affects the brain's connectivity has been greatly advanced by mapping topological alterations of large-scale brain networks (i.e., connectomes) using noninvasive neurophysiological and neuroimaging techniques (e.g., electroencephalograph, functional MRI, and diffusion MRI) in combination with graph theoretical approaches. In this review, we summarize the recent progresses of functional and structural brain connectomics in ADHD, focusing on graphic analysis of large-scale brain systems. Convergent evidence suggests that children with ADHD had abnormal small-world properties in both functional and structural brain networks characterized by higher local clustering and lower global integrity, suggesting a disorder-related shift of network topology toward regular configurations. Moreover, ADHD children showed the redistribution of regional nodes and connectivity involving the default-mode, attention, and sensorimotor systems. Importantly, these ADHD-associated alterations significantly correlated with behavior disturbances (e.g., inattention and hyperactivity/impulsivity symptoms) and exhibited differential patterns between clinical subtypes. Together, these connectome-based studies highlight brain network dysfunction in ADHD, thus opening up a new window into our understanding of the pathophysiological mechanisms of this disorder. These works might also have important implications on the development of imaging-based biomarkers for clinical diagnosis and treatment evaluation in ADHD.

Urea cycle disorders: brain MRI and neurological outcome.

PubMed

Bireley, William R; Van Hove, Johan L K; Gallagher, Renata C; Fenton, Laura Z

2012-04-01

Urea cycle disorders encompass several enzyme deficiencies that can result in cerebral damage, with a wide clinical spectrum from asymptomatic to severe. The goal of this study was to correlate brain MRI abnormalities in urea cycle disorders with clinical neurological sequelae to evaluate whether MRI abnormalities can assist in guiding difficult treatment decisions. We performed a retrospective chart review of patients with urea cycle disorders and symptomatic hyperammonemia. Brain MRI images were reviewed for abnormalities that correlated with severity of clinical neurological sequelae. Our case series comprises six urea cycle disorder patients, five with ornithine transcarbamylase deficiency and one with citrullinemia type 1. The observed trend in distribution of brain MRI abnormalities as the severity of neurological sequelae increased was the peri-insular region first, extending into the frontal, parietal, temporal and, finally, the occipital lobes. There was thalamic restricted diffusion in three children with prolonged hyperammonemia. Prior to death, this site is typically reported to be spared in urea cycle disorders. The pattern and extent of brain MRI abnormalities correlate with clinical neurological outcome in our case series. This suggests that brain MRI abnormalities may assist in determining prognosis and helping clinicians with subsequent treatment decisions.

Dipole source localization of event-related brain activity indicative of an early visual selective attention deficit in ADHD children.

PubMed

Jonkman, L M; Kenemans, J L; Kemner, C; Verbaten, M N; van Engeland, H

2004-07-01

This study was aimed at investigating whether attention-deficit hyperactivity disorder (ADHD) children suffer from specific early selective attention deficits in the visual modality with the aid of event-related brain potentials (ERPs). Furthermore, brain source localization was applied to identify brain areas underlying possible deficits in selective visual processing in ADHD children. A two-channel visual color selection task was administered to 18 ADHD and 18 control subjects in the age range of 7-13 years and ERP activity was derived from 30 electrodes. ADHD children exhibited lower perceptual sensitivity scores resulting in poorer target selection. The ERP data suggested an early selective-attention deficit as manifested in smaller frontal positive activity (frontal selection positivity; FSP) in ADHD children around 200 ms whereas later occipital and fronto-central negative activity (OSN and N2b; 200-400 ms latency) appeared to be unaffected. Source localization explained the FSP by posterior-medial equivalent dipoles in control subjects, which may reflect the contribution of numerous surrounding areas. ADHD children have problems with selective visual processing that might be caused by a specific early filtering deficit (absent FSP) occurring around 200 ms. The neural sources underlying these problems have to be further identified. Source localization also suggested abnormalities in the 200-400 ms time range, pertaining to the distribution of attention-modulated activity in lateral frontal areas.

Histological Characterization of the Irritative Zones in Focal Cortical Dysplasia Using a Preclinical Rat Model.

PubMed

Deshmukh, Abhay; Leichner, Jared; Bae, Jihye; Song, Yinchen; Valdés-Hernández, Pedro A; Lin, Wei-Chiang; Riera, Jorge J

2018-01-01

Current clinical practice in focal epilepsy involves brain source imaging (BSI) to localize brain areas where from interictal epileptiform discharges (IEDs) emerge. These areas, named irritative zones , have been useful to define candidate seizures-onset zones during pre-surgical workup. Since human histological data are mostly available from final resected zones, systematic studies characterizing pathophysiological mechanisms and abnormal molecular/cellular substrates in irritative zones-independent of them being epileptogenic-are challenging. Combining BSI and histological analysis from all types of irritative zones is only possible through the use of preclinical animal models. Here, we recorded 32-channel spontaneous electroencephalographic data from rats that have focal cortical dysplasia (FCD) and chronic seizures. BSI for different IED subtypes was performed using the methodology presented in Bae et al. (2015). Post-mortem brain sections containing irritative zones were stained to quantify anatomical, functional, and inflammatory biomarkers specific for epileptogenesis, and the results were compared with those obtained using the contralateral healthy brain tissue. We found abnormal anatomical structures in all irritative zones (i.e., larger neuronal processes, glioreactivity, and vascular cuffing) and larger expressions for neurotransmission (i.e., NR2B) and inflammation (i.e., ILβ1, TNFα and HMGB1). We conclude that irritative zones in this rat preclinical model of FCD comprise abnormal tissues disregarding whether they are actually involved in icto-genesis or not. We hypothesize that seizure perpetuation happens gradually; hence, our results could support the use of IED-based BSI for the early diagnosis and preventive treatment of potential epileptic foci. Further verifications in humans are yet needed.

Abnormalities of functional brain networks in pathological gambling: a graph-theoretical approach

PubMed Central

Tschernegg, Melanie; Crone, Julia S.; Eigenberger, Tina; Schwartenbeck, Philipp; Fauth-Bühler, Mira; Lemènager, Tagrid; Mann, Karl; Thon, Natasha; Wurst, Friedrich M.; Kronbichler, Martin

2013-01-01

Functional neuroimaging studies of pathological gambling (PG) demonstrate alterations in frontal and subcortical regions of the mesolimbic reward system. However, most investigations were performed using tasks involving reward processing or executive functions. Little is known about brain network abnormalities during task-free resting state in PG. In the present study, graph-theoretical methods were used to investigate network properties of resting state functional magnetic resonance imaging data in PG. We compared 19 patients with PG to 19 healthy controls (HCs) using the Graph Analysis Toolbox (GAT). None of the examined global metrics differed between groups. At the nodal level, pathological gambler showed a reduced clustering coefficient in the left paracingulate cortex and the left juxtapositional lobe (supplementary motor area, SMA), reduced local efficiency in the left SMA, as well as an increased node betweenness for the left and right paracingulate cortex and the left SMA. At an uncorrected threshold level, the node betweenness in the left inferior frontal gyrus was decreased and increased in the caudate. Additionally, increased functional connectivity between fronto-striatal regions and within frontal regions has also been found for the gambling patients. These findings suggest that regions associated with the reward system demonstrate reduced segregation but enhanced integration while regions associated with executive functions demonstrate reduced integration. The present study makes evident that PG is also associated with abnormalities in the topological network structure of the brain during rest. Since alterations in PG cannot be explained by direct effects of abused substances on the brain, these findings will be of relevance for understanding functional connectivity in other addictive disorders. PMID:24098282

[Forensic application of brainstem auditory evoked potential in patients with brain concussion].

PubMed

Zheng, Xing-Bin; Li, Sheng-Yan; Huang, Si-Xing; Ma, Ke-Xin

2008-12-01

To investigate changes of brainstem auditory evoked potential (BAEP) in patients with brain concussion. Nineteen patients with brain concussion were studied with BAEP examination. The data was compared to the healthy persons reported in literatures. The abnormal rate of BAEP for patients with brain concussion was 89.5%. There was a statistically significant difference between the abnormal rate of patients and that of healthy persons (P<0.05). The abnormal rate of BAEP in the brainstem pathway for patients with brain concussion was 73.7%, indicating dysfunction of the brainstem in those patients. BAEP might be helpful in forensic diagnosis of brain concussion.

Comparison of SPET brain perfusion and 18F-FDG brain metabolism in patients with chronic fatigue syndrome.

PubMed

Abu-Judeh, H H; Levine, S; Kumar, M; el-Zeftawy, H; Naddaf, S; Lou, J Q; Abdel-Dayem, H M

1998-11-01

Chronic fatigue syndrome is a clinically defined condition of uncertain aetiology. We compared 99Tcm-HMPAO single photon emission tomography (SPET) brain perfusion with dual-head 18F-FDG brain metabolism in patients with chronic fatigue syndrome. Eighteen patients (14 females, 4 males), who fulfilled the diagnostic criteria of the Centers for Disease Control for chronic fatigue syndrome, were investigated. Thirteen patients had abnormal SPET brain perfusion scans and five had normal scans. Fifteen patients had normal glucose brain metabolism scans and three had abnormal scans. We conclude that, in chronic fatigue syndrome patients, there is discordance between SPET brain perfusion and 18F-FDG brain uptake. It is possible to have brain perfusion abnormalities without corresponding changes in glucose uptake.

3D PATTERN OF BRAIN ABNORMALITIES IN FRAGILE X SYNDROME VISUALIZED USING TENSOR-BASED MORPHOMETRY

PubMed Central

Lee, Agatha D.; Leow, Alex D.; Lu, Allen; Reiss, Allan L.; Hall, Scott; Chiang, Ming-Chang; Toga, Arthur W.; Thompson, Paul M.

2007-01-01

Fragile X syndrome (FraX), a genetic neurodevelopmental disorder, results in impaired cognition with particular deficits in executive function and visuo-spatial skills. Here we report the first detailed 3D maps of the effects of the Fragile X mutation on brain structure, using tensor-based morphometry. TBM visualizes structural brain deficits automatically, without time-consuming specification of regions-of-interest. We compared 36 subjects with FraX (age: 14.66+/−1.58SD, 18 females/18 males), and 33 age-matched healthy controls (age: 14.67+/−2.2SD, 17 females/16 males), using high-dimensional elastic image registration. All 69 subjects' 3D T1-weighted brain MRIs were spatially deformed to match a high-resolution single-subject average MRI scan in ICBM space, whose geometry was optimized to produce a minimal deformation target. Maps of the local Jacobian determinant (expansion factor) were computed from the deformation fields. Statistical maps showed increased caudate (10% higher; p=0.001) and lateral ventricle volumes (19% higher; p=0.003), and trend-level parietal and temporal white matter excesses (10% higher locally; p=0.04). In affected females, volume abnormalities correlated with reduction in systemically measured levels of the fragile X mental retardation protein (FMRP; Spearman's r<−0.5 locally). Decreased FMRP correlated with ventricular expansion (p=0.042; permutation test), and anterior cingulate tissue reductions (p=0.0026; permutation test) supporting theories that FMRP is required for normal dendritic pruning in fronto-striatal-limbic pathways. No sex differences were found; findings were confirmed using traditional volumetric measures in regions of interest. Deficit patterns were replicated using Lie group statistics optimized for tensor-valued data. Investigation of how these anomalies emerge over time will accelerate our understanding of FraX and its treatment. PMID:17161622

Brain Injury in Neonates with Complex Congenital Heart Disease: What Is the Predictive Value of MRI in the Fetal Period?

PubMed

Brossard-Racine, M; du Plessis, A; Vezina, G; Robertson, R; Donofrio, M; Tworetzky, W; Limperopoulos, C

2016-07-01

Brain injury in neonates with congenital heart disease is an important predictor of adverse neurodevelopmental outcome. Impaired brain development in congenital heart disease may have a prenatal origin, but the sensitivity and specificity of fetal brain MR imaging for predicting neonatal brain lesions are currently unknown. We sought to determine the value of conventional fetal MR imaging for predicting abnormal findings on neonatal preoperative MR imaging in neonates with complex congenital heart disease. MR imaging studies were performed in 103 fetuses with confirmed congenital heart disease (mean gestational age, 31.57 ± 3.86 weeks) and were repeated postnatally before cardiac surgery (mean age, 6.8 ± 12.2 days). Each MR imaging study was read by a pediatric neuroradiologist. Brain abnormalities were detected in 17/103 (16%) fetuses by fetal MR imaging and in 33/103 (32%) neonates by neonatal MR imaging. Only 9/33 studies with abnormal neonatal findings were preceded by abnormal findings on fetal MR imaging. The sensitivity and specificity of conventional fetal brain MR imaging for predicting neonatal brain abnormalities were 27% and 89%, respectively. Brain abnormalities detected by in utero MR imaging in fetuses with congenital heart disease are associated with higher risk of postnatal preoperative brain injury. However, a substantial proportion of anomalies on postnatal MR imaging were not present on fetal MR imaging; this result is likely due to the limitations of conventional fetal MR imaging and the emergence of new lesions that occurred after the fetal studies. Postnatal brain MR imaging studies are needed to confirm the presence of injury before open heart surgery. © 2016 by American Journal of Neuroradiology.

MRI as a tool to study brain structure from mouse models for mental retardation

NASA Astrophysics Data System (ADS)

Verhoye, Marleen; Sijbers, Jan; Kooy, R. F.; Reyniers, E.; Fransen, E.; Oostra, B. A.; Willems, Peter; Van der Linden, Anne-Marie

1998-07-01

Nowadays, transgenic mice are a common tool to study brain abnormalities in neurological disorders. These studies usually rely on neuropathological examinations, which have a number of drawbacks, including the risk of artefacts introduced by fixation and dehydration procedures. Here we present 3D Fast Spin Echo Magnetic Resonance Imaging (MRI) in combination with 2D and 3D segmentation techniques as a powerful tool to study brain anatomy. We set up MRI of the brain in mouse models for the fragile X syndrome (FMR1 knockout) and Corpus callosum hypoplasia, mental Retardation, Adducted thumbs, Spastic paraplegia and Hydrocephalus (CRASH) syndrome (L1CAM knockout). Our major goal was to determine qualitative and quantitative differences in specific brain structures. MRI of the brain of fragile X and CRASH patients has revealed alterations in the size of specific brain structures, including the cerebellar vermis and the ventricular system. In the present MRI study of the brain from fragile X knockout mice, we have measured the size of the brain, cerebellum and 4th ventricle, which were reported as abnormal in human fragile X patients, but found no evidence for altered brain regions in the mouse model. In CRASH syndrome, the most specific brain abnormalities are vermis hypoplasia and abnormalities of the ventricular system with some degree of hydrocephalus. With the MRI study of L1CAM knockout mice we found vermis hypoplasia, abnormalities of the ventricular system including dilatation of the lateral and the 4th ventricles. These subtle abnormalities were not detected upon standard neuropathological examination. Here we proved that this sensitive MRI technique allows to measure small differences which can not always be detected by means of pathology.

Altered local spontaneous activity in frontal lobe epilepsy: a resting-state functional magnetic resonance imaging study.

PubMed

Dong, Li; Li, Hechun; He, Zhongqiong; Jiang, Sisi; Klugah-Brown, Benjamin; Chen, Lin; Wang, Pu; Tan, Song; Luo, Cheng; Yao, Dezhong

2016-11-01

The purpose of this study was to investigate the local spatiotemporal consistency of spontaneous brain activity in patients with frontal lobe epilepsy (FLE). Eyes closed resting-state functional magnetic resonance imaging (fMRI) data were collected from 19 FLE patients and 19 age- and gender-matched healthy controls. A novel measure, named FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) was used to assess the spatiotemporal consistency of local spontaneous activity (emphasizing both local temporal homogeneity and regional stability of brain activity states). Then, two-sample t test was performed to detect the FOCA differences between two groups. Partial correlations between the FOCA values and durations of epilepsy were further analyzed. Compared with controls, FLE patients demonstrated increased FOCA in distant brain regions including the frontal and parietal cortices, as well as the basal ganglia. The decreased FOCA was located in the temporal cortex, posterior default model regions, and cerebellum. In addition, the FOCA measure was linked to the duration of epilepsy in basal ganglia. Our study suggested that alterations of local spontaneous activity in frontoparietal cortex and basal ganglia was associated with the pathophysiology of FLE; and the abnormality in frontal and default model regions might account for the potential cognitive impairment in FLE. We also presumed that the FOCA measure had potential to provide important insights into understanding epilepsy such as FLE.

Glial dysfunction in abstinent methamphetamine abusers

PubMed Central

Sailasuta, Napapon; Abulseoud, Osama; Harris, Kent C; Ross, Brian D

2010-01-01

Persistent neurochemical abnormalities in frontal brain structures are believed to result from methamphetamine use. We developed a localized 13C magnetic resonance spectroscopy (MRS) assay on a conventional MR scanner, to quantify selectively glial metabolic flux rate in frontal brain of normal subjects and a cohort of recovering abstinent methamphetamine abusers. Steady-state bicarbonate concentrations were similar, between 11 and 15 mmol/L in mixed gray-white matter of frontal brain of normal volunteers and recovering methamphetamine-abusing subjects (P>0.1). However, glial 13C-bicarbonate production rate from [1-13C]acetate, equating with glial tricarboxylic acid (TCA) cycle rate, was significantly reduced in frontal brain of abstinent methamphetamine-addicted women (methamphetamine 0.04 μmol/g per min (N=5) versus controls 0.11 μmol/g per min (N=5), P=0.001). This is equivalent to 36% of the normal glial TCA cycle rate. Severe reduction in glial TCA cycle rate that normally comprises 10% of total cerebral metabolic rate may impact operation of the neuronal glial glutamate cycle and result in accumulation of frontal brain glutamate, as observed in these recovering methamphetamine abusers. Although these are the first studies to define directly an abnormality in glial metabolism in human methamphetamine abuse, sequential studies using analogous 13C MRS methods may determine ‘cause and effect' between glial failure and neuronal injury. PMID:20040926

[INDIVIDUAL EVALUATION OF LORETA ABNORMALITIES IN IDIOPATHIC GENERALIZED EPILEPSY].

PubMed

Clemens, Béla; Puskás, Szilvia; Besenyei, Mónika; Kondákor, István; Hollódy, Katalin; Fogarasi, Andrós; Bense, Katalin; Emri, Miklós; Opposits Gábor; Kovács, Noémi Zsuzsanna; Fekete, István

2016-03-30

Contemporary neuroimaging methods disclosed structural and functional cerebral abnormalities in idiopathic generalized epilepsies (IGEs). However, individual electrical (EEG) abnormalities have not been evaluated yet in IGE patients. IGE patients were investigated in the drug-free condition and after 3-6 month of antiepileptic treatment. To estimate the reproducibility of qEEG variables a retrospective recruited cohort of IGE patients was investigated. 19-channel resting state EEG activity was recorded. For each patient a total of 2 minutes EEG activity was analyzed by LORETA (Low Resolution Electromagnetic Tomography). Raw LORETA values were Z-transformed and projected to a MRI template. Z-values outside within the [+3Z] to [-3Z] range were labelled as statistically abnormal. 1. In drug-free condition, 41-50% of IGE patients showed abnormal LORETA values. 2. Abnormal LORETA findings showed great inter-individual variability. 3. Most abnormal LORETA-findings were symmetrical. 4. Most maximum Z-values were localized to frontal or temporal cortex. 5. Succesfull treatment was mostly coupled with disappearence of LORETA-abnormality, persistent seizures were accompanied by persistent LORETA abnormality. 1. LORETA abnormalities detected in the untreated condition reflect seizure-generating property of the cortex in IGE patients. 2. Maximum LORETA-Z abnormalities were topographically congruent with structural abnormalities reported by other research groups. 3. LORETA might help to investigate drug effects at the whole-brain level.

[Study on Abnormal Topological Properties of Structural Brain Networks of Patients with Depression Comorbid with Anxiety].

PubMed

Wu, Xiuyong; Wu, Xiaoming; Peng, Hongjun; Ning, Yuping; Wu, Kai

2016-06-01

This paper is aimed to analyze the topological properties of structural brain networks in depressive patients with and without anxiety and to explore the neuropath logical mechanisms of depression comorbid with anxiety.Diffusion tensor imaging and deterministic tractography were applied to map the white matter structural networks.We collected 20 depressive patients with anxiety(DPA),18 depressive patients without anxiety(DP),and 28 normal controls(NC)as comparative groups.The global and nodal properties of the structural brain networks in the three groups were analyzed with graph theoretical methods.The result showed that1 the structural brain networks in three groups showed small-world properties and highly connected global hubs predominately from association cortices;2DP group showed lower local efficiency and global efficiency compared to NC group,whereas DPA group showed higher local efficiency and global efficiency compared to NC group;3significant differences of network properties(clustering coefficient,characteristic path lengths,local efficiency,global efficiency)were found between DPA and DP groups;4DP group showed significant changes of nodal efficiency in the brain areas primarily in the temporal lobe and bilateral frontal gyrus,compared to DPA and NC groups.The analysis indicated that the DP and DPA groups showed nodal properties of the structural brain networks,compared to NC group.Moreover,the two diseased groups indicated an opposite trend in the network properties.The results of this study may provide a new imaging index for clinical diagnosis for depression comorbid with anxiety.

Impaired coupling of local and global functional feedbacks underlies abnormal synchronization and negative symptoms of schizophrenia.

PubMed

Noh, Kyungchul; Shin, Kyung Soon; Shin, Dongkwan; Hwang, Jae Yeon; Kim, June Sic; Jang, Joon Hwan; Chung, Chun Kee; Kwon, Jun Soo; Cho, Kwang-Hyun

2013-04-10

Abnormal synchronization of brain oscillations is found to be associated with various core symptoms of schizophrenia. However, the underlying mechanism of this association remains yet to be elucidated. In this study, we found that coupled local and global feedback (CLGF) circuits in the cortical functional network are related to the abnormal synchronization and also correlated to the negative symptom of schizophrenia. Analysis of the magnetoencephalography data obtained from patients with chronic schizophrenia during rest revealed an increase in beta band synchronization and a reduction in gamma band power compared to healthy controls. Using a feedback identification method based on non-causal impulse responses, we constructed functional feedback networks and found that CLGF circuits were significantly reduced in schizophrenia. From computational analysis on the basis of the Wilson-Cowan model, we unraveled that the CLGF circuits are critically involved in the abnormal synchronization and the dynamical switching between beta and gamma bands power in schizophrenia. Moreover, we found that the abundance of CLGF circuits was negatively correlated with the development of negative symptoms of schizophrenia, suggesting that the negative symptom is closely related to the impairment of this circuit. Our study implicates that patients with schizophrenia might have the impaired coupling of inter- and intra-regional functional feedbacks and that the CLGF circuit might serve as a critical bridge between abnormal synchronization and the negative symptoms of schizophrenia.

Structural brain abnormalities in Cushing's syndrome.

PubMed

Bauduin, Stephanie E E C; van der Wee, Nic J A; van der Werff, Steven J A

2018-05-08

Alongside various physical symptoms, patients with Cushing's disease and Cushing's syndrome display a wide variety of neuropsychiatric and cognitive symptoms, which are indicative of involvement of the central nervous system. The aim of this review is to provide an overview of the structural brain abnormalities that are associated with Cushing's disease and Cushing's syndrome and their relation to behavioral and cognitive symptomatology. In this review, we discuss the gray matter structural abnormalities found in patients with active Cushing's disease and Cushing's syndrome, the reversibility and persistence of these changes and the white matter structural changes related to Cushing's syndrome. Recent findings are of particular interest because they provide more detailed information on localization of the structural changes as well as possible insights into the underlying biological processes. Active Cushing's disease and Cushing's syndrome is related to volume reductions of the hippocampus and in a prefrontal region involving the anterior cingulate cortex (ACC) and medial frontal gyrus (MFG). Whilst there are indications that the reductions in hippocampal volume are partially reversible, the changes in the ACC and MFG appear to be more persistent. In contrast to the volumetric findings, changes in white matter connectivity are typically widespread involving multiple tracts.

Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects

NASA Astrophysics Data System (ADS)

Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

2017-08-01

Objective. Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. Approach. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. Main results. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. Significance. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

Effective brain network analysis with resting-state EEG data: a comparison between heroin abstinent and non-addicted subjects.

PubMed

Hu, Bin; Dong, Qunxi; Hao, Yanrong; Zhao, Qinglin; Shen, Jian; Zheng, Fang

2017-08-01

Neuro-electrophysiological tools have been widely used in heroin addiction studies. Previous studies indicated that chronic heroin abuse would result in abnormal functional organization of the brain, while few heroin addiction studies have applied the effective connectivity tool to analyze the brain functional system (BFS) alterations induced by heroin abuse. The present study aims to identify the abnormality of resting-state heroin abstinent BFS using source decomposition and effective connectivity tools. The resting-state electroencephalograph (EEG) signals were acquired from 15 male heroin abstinent (HA) subjects and 14 male non-addicted (NA) controls. Multivariate autoregressive models combined independent component analysis (MVARICA) was applied for blind source decomposition. Generalized partial directed coherence (GPDC) was applied for effective brain connectivity analysis. Effective brain networks of both HA and NA groups were constructed. The two groups of effective cortical networks were compared by the bootstrap method. Abnormal causal interactions between decomposed source regions were estimated in the 1-45 Hz frequency domain. This work suggested: (a) there were clear effective network alterations in heroin abstinent subject groups; (b) the parietal region was a dominant hub of the abnormally weaker causal pathways, and the left occipital region was a dominant hub of the abnormally stronger causal pathways. These findings provide direct evidence that chronic heroin abuse induces brain functional abnormalities. The potential value of combining effective connectivity analysis and brain source decomposition methods in exploring brain alterations of heroin addicts is also implied.

Deep Brain Stimulation

PubMed Central

Lyketsos, Constantine G.; Pendergrass, Jo Cara; Lozano, Andres M.

2012-01-01

Recent studies have identified an association between memory deficits and defects of the integrated neuronal cortical areas known collectively as the default mode network. It is conceivable that the amyloid deposition or other molecular abnormalities seen in patients with Alzheimer’s disease may interfere with this network and disrupt neuronal circuits beyond the localized brain areas. Therefore, Alzheimer’s disease may be both a degenerative disease and a broader system-level disorder affecting integrated neuronal pathways involved in memory. In this paper, we describe the rationale and provide some evidence to support the study of deep brain stimulation of the hippocampal fornix as a novel treatment to improve neuronal circuitry within these integrated networks and thereby sustain memory function in early Alzheimer’s disease. PMID:23346514

Is the Internet gaming-addicted brain close to be in a pathological state?

PubMed

Park, Chang-Hyun; Chun, Ji-Won; Cho, Huyn; Jung, Young-Chul; Choi, Jihye; Kim, Dai Jin

2017-01-01

Internet gaming addiction (IGA) is becoming a common and widespread mental health concern. Although IGA induces a variety of negative psychosocial consequences, it is yet ambiguous whether the brain addicted to Internet gaming is considered to be in a pathological state. We investigated IGA-induced abnormalities of the brain specifically from the network perspective and qualitatively assessed whether the Internet gaming-addicted brain is in a state similar to the pathological brain. Topological properties of brain functional networks were examined by applying a graph-theoretical approach to analyzing functional magnetic resonance imaging data acquired during a resting state in 19 IGA adolescents and 20 age-matched healthy controls. We compared functional distance-based measures, global and local efficiency of resting state brain functional networks between the two groups to assess how the IGA subjects' brain was topologically altered from the controls' brain. The IGA subjects had severer impulsiveness and their brain functional networks showed higher global efficiency and lower local efficiency relative to the controls. These topological differences suggest that IGA induced brain functional networks to shift toward the random topological architecture, as exhibited in other pathological states. Furthermore, for the IGA subjects, the topological alterations were specifically attributable to interregional connections incident on the frontal region, and the degree of impulsiveness was associated with the topological alterations over the frontolimbic connections. The current findings lend support to the proposition that the Internet gaming-addicted brain could be in the state similar to pathological states in terms of topological characteristics of brain functional networks. © 2015 Society for the Study of Addiction.

Ketamine changes the local resting-state functional properties of anesthetized-monkey brain.

PubMed

Rao, Jia-Sheng; Liu, Zuxiang; Zhao, Can; Wei, Rui-Han; Zhao, Wen; Tian, Peng-Yu; Zhou, Xia; Yang, Zhao-Yang; Li, Xiao-Guang

2017-11-01

Ketamine is a well-known anesthetic. 'Recreational' use of ketamine common induces psychosis-like symptoms and cognitive impairments. The acute and chronic effects of ketamine on relevant brain circuits have been studied, but the effects of single-dose ketamine administration on the local resting-state functional properties of the brain remain unknown. In this study, we aimed to assess the effects of single-dose ketamine administration on the brain local intrinsic properties. We used resting-state functional magnetic resonance imaging (rs-fMRI) to explore the ketamine-induced alterations of brain intrinsic properties. Seven adult rhesus monkeys were imaged with rs-fMRI to examine the fractional amplitude of low-frequency fluctuation (fALFF) and regional homogeneity (ReHo) in the brain before and after ketamine injection. Paired comparisons were used to detect the significantly altered regions. Results showed that the fALFF of the prefrontal cortex (p=0.046), caudate nucleus (left side, p=0.018; right side, p=0.025), and putamen (p=0.020) in post-injection stage significantly increased compared with those in pre-injection period. The ReHo of nucleus accumbens (p=0.049), caudate nucleus (p=0.037), and hippocampus (p=0.025) increased after ketamine injection, but that of prefrontal cortex decreased (p<0.05). These findings demonstrated that single-dose ketamine administration can change the regional intensity and synchronism of brain activity, thereby providing evidence of ketamine-induced abnormal resting-state functional properties in primates. This evidence may help further elucidate the effects of ketamine on the cerebral resting status. Copyright © 2017. Published by Elsevier Inc.

Isolated cortical visual loss with subtle brain MRI abnormalities in a case of hypoxic-ischemic encephalopathy.

PubMed

Margolin, Edward; Gujar, Sachin K; Trobe, Jonathan D

2007-12-01

A 16-year-old boy who was briefly asystolic and hypotensive after a motor vehicle accident complained of abnormal vision after recovering consciousness. Visual acuity was normal, but visual fields were severely constricted without clear hemianopic features. The ophthalmic examination was otherwise normal. Brain MRI performed 11 days after the accident showed no pertinent abnormalities. At 6 months after the event, brain MRI demonstrated brain volume loss in the primary visual cortex and no other abnormalities. One year later, visual fields remained severely constricted; neurologic examination, including formal neuropsychometric testing, was normal. This case emphasizes the fact that hypoxic-ischemic encephalopathy (HIE) may cause enduring damage limited to primary visual cortex and that the MRI abnormalities may be subtle. These phenomena should be recognized in the management of patients with HIE.

Clinical and mutational spectrum in Korean patients with Rubinstein-Taybi syndrome: the spectrum of brain MRI abnormalities.

PubMed

Lee, Jin Sook; Byun, Christine K; Kim, Hunmin; Lim, Byung Chan; Hwang, Hee; Choi, Ji Eun; Hwang, Yong Seung; Seong, Moon-Woo; Park, Sung Sup; Kim, Ki Joong; Chae, Jong-Hee

2015-04-01

Rubinstein-Taybi syndrome (RSTS) is one of the neurodevelopmental disorders caused by mutations of epigenetic genes. The CREBBP gene is the most common causative gene, encoding the CREB-binding protein with histone acetyltransferase (HAT) activity, an epigenetic modulator. To date, there have been few reports on the structural abnormalities of the brain in RSTS patients. In addition, there are no reports on the analysis of CREBBP mutations in Korean RSTS patients. We performed mutational analyses on 16 unrelated patients with RSTS, with diagnosis based on the typical clinical features. Their medical records and brain MRI images were reviewed retrospectively. Ten of 16 patients (62.5%) had mutations in the CREBBP gene. The mutations included five frameshift mutations (31.2%), two nonsense mutations (12.5%), and three multiexon deletions (18.8%). There were no remarkable significant differences in the clinical features between those with and without a CREBBP mutation, although brain MRI abnormalities were more frequently observed in those with a CREBBP mutation. Seven of 10 patients in whom brain imaging was performed had structural abnormalities, including Chiari malformation type 1, thinning of the corpus callosum, and delayed myelination. There were no differences in delayed development or cognitive impairment between those with and without abnormal brain images, while epilepsy was involved in two patients who had abnormalities on brain MRI images. We investigated the spectrum of CREBBP mutations in Korean patients with RSTS for the first time. Eight novel mutations extended the genetic spectrum of CREBBP mutations in RSTS patients. This is also the first study showing the prevalence and spectrum of abnormalities on brain MRI in RSTS patients. Copyright © 2014 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Impact of brain injury on functional measures of amplitude-integrated EEG at term equivalent age in premature infants.

PubMed

El Ters, N M; Vesoulis, Z A; Liao, S M; Smyser, C D; Mathur, A M

2017-08-01

To evaluate the association between qualitative and quantitative amplitude-integrated EEG (aEEG) measures at term equivalent age (TEA) and brain injury on magnetic resonance imaging (MRI) in preterm infants. A cohort of premature infants born at <30 weeks of gestation and with moderate-to-severe MRI injury on a TEA MRI scan was identified. A contemporaneous group of gestational age-matched control infants also born at <30 weeks of gestation with none/mild injury on MRI was also recruited. Quantitative aEEG measures, including maximum and minimum amplitudes, bandwidth span and spectral edge frequency (SEF 90 ), were calculated using an offline software package. The aEEG recordings were qualitatively scored using the Burdjalov system. MRI scans, performed on the same day as aEEG, occurred at a mean postmenstrual age of 38.0 (range 37 to 42) weeks and were scored for abnormality in a blinded manner using an established MRI scoring system. Twenty-eight (46.7%) infants had a normal MRI or mild brain abnormality, while 32 (53.3%) infants had moderate-to-severe brain abnormality. Univariate regression analysis demonstrated an association between severity of brain abnormality and quantitative measures of left and right SEF 90 and bandwidth span (β=-0.38, -0.40 and 0.30, respectively) and qualitative measures of cyclicity, continuity and total Burdjalov score (β=-0.10, -0.14 and -0.12, respectively). After correcting for confounding variables, the relationship between MRI abnormality score and aEEG measures of SEF 90 , bandwidth span and Burdjalov score remained significant. Brain abnormalities on MRI at TEA in premature infants are associated with abnormalities on term aEEG measures, suggesting that anatomical brain injury may contribute to delay in functional brain maturation as assessed using aEEG.

Effects of gamma-aminobutyric acid-modulating drugs on working memory and brain function in patients with schizophrenia.

PubMed

Menzies, Lara; Ooi, Cinly; Kamath, Shri; Suckling, John; McKenna, Peter; Fletcher, Paul; Bullmore, Ed; Stephenson, Caroline

2007-02-01

Cognitive impairment causes morbidity in schizophrenia and could be due to abnormalities of cortical interneurons using the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). To test the predictions that cognitive and brain functional responses to GABA-modulating drugs are correlated and abnormal in schizophrenia. Pharmacological functional magnetic resonance imaging study of 2 groups, each undergoing scanning 3 times, using an N-back working memory task, after placebo, lorazepam, or flumazenil administration. Eleven patients with chronic schizophrenia were recruited from a rehabilitation service, and 11 healthy volunteers matched for age, sex, and premorbid IQ were recruited from the local community. Intervention Participants received 2 mg of oral lorazepam, a 0.9-mg intravenous flumazenil bolus followed by a flumazenil infusion of 0.0102 mg/min, or oral and intravenous placebo. Working memory performance was summarized by the target discrimination index at several levels of difficulty. Increasing (or decreasing) brain functional activation in response to increasing task difficulty was summarized by the positive (or negative) load response. Lorazepam impaired performance and flumazenil enhanced it; these cognitive effects were more salient in schizophrenic patients. Functional magnetic resonance imaging demonstrated positive load response in a frontoparietal system and negative load response in the temporal and posterior cingulate regions; activation of the frontoparietal cortex was positively correlated with deactivation of the temporocingulate cortex. After placebo administration, schizophrenic patients had abnormally attenuated activation of the frontoparietal cortex and deactivation of the temporocingulate cortex; this pattern was mimicked in healthy volunteers and exacerbated in schizophrenic patients by lorazepam. However, in schizophrenic patients, flumazenil enhanced deactivation of the temporocingulate and activation of the anterior cingulate cortices. The GABA-modulating drugs differentially affect working memory performance and brain function in schizophrenia. Cognitive impairment in schizophrenia may reflect abnormal inhibitory function and could be treated by drugs targeting GABA neurotransmission.

Self-regulation of brain oscillations as a treatment for aberrant brain connections in children with autism.

PubMed

Pineda, J A; Juavinett, A; Datko, M

2012-12-01

Autism is a highly varied developmental disorder typically characterized by deficits in reciprocal social interaction, difficulties with verbal and nonverbal communication, and restricted interests and repetitive behaviors. Although a wide range of behavioral, pharmacological, and alternative medicine strategies have been reported to ameliorate specific symptoms for some individuals, there is at present no cure for the condition. Nonetheless, among the many incompatible observations about aspects of the development, anatomy, and functionality of the autistic brain, it is widely agreed that it is characterized by widespread aberrant connectivity. Such disordered connectivity, be it increased, decreased, or otherwise compromised, may complicate healthy synchronization and communication among and within different neural circuits, thereby producing abnormal processing of sensory inputs necessary for normal social life. It is widely accepted that the innate properties of brain electrical activity produce pacemaker elements and linked networks that oscillate synchronously or asynchronously, likely reflecting a type of functional connectivity. Using phase coherence in multiple frequency EEG bands as a measure of functional connectivity, studies have shown evidence for both global hypoconnectivity and local hyperconnectivity in individuals with ASD. However, the nature of the brain's experience-dependent structural plasticity suggests that these abnormal patterns may be reversed with the proper type of treatment. Indeed, neurofeedback (NF) training, an intervention based on operant conditioning that results in self-regulation of brain electrical oscillations, has shown promise in addressing marked abnormalities in functional and structural connectivity. It is hypothesized that neurofeedback produces positive behavioral changes in ASD children by normalizing the aberrant connections within and between neural circuits. NF exploits the brain's plasticity to normalize aberrant connectivity patterns apparent in the autistic brain. By grounding this training in known anatomical (e.g., mirror neuron system) and functional markers (e.g., mu rhythms) of autism, NF training holds promise to support current treatments for this complex disorder. The proposed hypothesis specifically states that neurofeedback-induced alpha mu (8-12Hz) rhythm suppression or desynchronization, a marker of cortical activation, should induce neuroplastic changes and lead to normalization in relevant mirroring networks that have been associated with higher-order social cognition. Copyright © 2012 Elsevier Ltd. All rights reserved.

Dynamic Reorganization of Functional Connectivity Reveals Abnormal Temporal Efficiency in Schizophrenia.

PubMed

Sun, Yu; Collinson, Simon L; Suckling, John; Sim, Kang

2018-06-07

Emerging evidence suggests that schizophrenia is associated with brain dysconnectivity. Nonetheless, the implicit assumption of stationary functional connectivity (FC) adopted in most previous resting-state functional magnetic resonance imaging (fMRI) studies raises an open question of schizophrenia-related aberrations in dynamic properties of resting-state FC. This study introduces an empirical method to examine the dynamic functional dysconnectivity in patients with schizophrenia. Temporal brain networks were estimated from resting-state fMRI of 2 independent datasets (patients/controls = 18/19 and 53/57 for self-recorded dataset and a publicly available replication dataset, respectively) by the correlation of sliding time-windowed time courses among regions of a predefined atlas. Through the newly introduced temporal efficiency approach and temporal random network models, we examined, for the first time, the 3D spatiotemporal architecture of the temporal brain network. We found that although prominent temporal small-world properties were revealed in both groups, temporal brain networks of patients with schizophrenia in both datasets showed a significantly higher temporal global efficiency, which cannot be simply attributable to head motion and sampling error. Specifically, we found localized changes of temporal nodal properties in the left frontal, right medial parietal, and subcortical areas that were associated with clinical features of schizophrenia. Our findings demonstrate that altered dynamic FC may underlie abnormal brain function and clinical symptoms observed in schizophrenia. Moreover, we provide new evidence to extend the dysconnectivity hypothesis in schizophrenia from static to dynamic brain network and highlight the potential of aberrant brain dynamic FC in unraveling the pathophysiologic mechanisms of the disease.

Diffusion tensor imaging with tract-based spatial statistics reveals local white matter abnormalities in preterm infants.

PubMed

Anjari, Mustafa; Srinivasan, Latha; Allsop, Joanna M; Hajnal, Joseph V; Rutherford, Mary A; Edwards, A David; Counsell, Serena J

2007-04-15

Infants born preterm have a high incidence of neurodevelopmental impairment in later childhood, often associated with poorly defined cerebral white matter abnormalities. Diffusion tensor imaging quantifies the diffusion of water within tissues and can assess microstructural abnormalities in the developing preterm brain. Tract-based spatial statistics (TBSS) is an automated observer-independent method of aligning fractional anisotropy (FA) images from multiple subjects to allow groupwise comparisons of diffusion tensor imaging data. We applied TBSS to test the hypothesis that preterm infants have reduced fractional anisotropy in specific regions of white matter compared to term-born controls. We studied 26 preterm infants with no evidence of focal lesions on conventional magnetic resonance imaging (MRI) at term equivalent age and 6 healthy term-born control infants. We found that the centrum semiovale, frontal white matter and the genu of the corpus callosum showed significantly lower FA in the preterm group. Infants born at less than or equal to 28 weeks gestational age (n=11) displayed additional reductions in FA in the external capsule, the posterior aspect of the posterior limb of the internal capsule and the isthmus and middle portion of the body of the corpus callosum. This study demonstrates that TBSS provides an observer-independent method of identifying white matter abnormalities in the preterm brain at term equivalent age in the absence of focal lesions.

Quantitative Folding Pattern Analysis of Early Primary Sulci in Human Fetuses with Brain Abnormalities.

PubMed

Im, K; Guimaraes, A; Kim, Y; Cottrill, E; Gagoski, B; Rollins, C; Ortinau, C; Yang, E; Grant, P E

2017-07-01

Aberrant gyral folding is a key feature in the diagnosis of many cerebral malformations. However, in fetal life, it is particularly challenging to confidently diagnose aberrant folding because of the rapid spatiotemporal changes of gyral development. Currently, there is no resource to measure how an individual fetal brain compares with normal spatiotemporal variations. In this study, we assessed the potential for automatic analysis of early sulcal patterns to detect individual fetal brains with cerebral abnormalities. Triplane MR images were aligned to create a motion-corrected volume for each individual fetal brain, and cortical plate surfaces were extracted. Sulcal basins were automatically identified on the cortical plate surface and compared with a combined set generated from 9 normal fetal brain templates. Sulcal pattern similarities to the templates were quantified by using multivariate geometric features and intersulcal relationships for 14 normal fetal brains and 5 fetal brains that were proved to be abnormal on postnatal MR imaging. Results were compared with the gyrification index. Significantly reduced sulcal pattern similarities to normal templates were found in all abnormal individual fetuses compared with normal fetuses (mean similarity [normal, abnormal], left: 0.818, 0.752; P < .001; right: 0.810, 0.753; P < .01). Altered location and depth patterns of sulcal basins were the primary distinguishing features. The gyrification index was not significantly different between the normal and abnormal groups. Automated analysis of interrelated patterning of early primary sulci could outperform the traditional gyrification index and has the potential to quantitatively detect individual fetuses with emerging abnormal sulcal patterns. © 2017 by American Journal of Neuroradiology.

Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) type I.

PubMed

Walton, K D; Dubois, M; Llinás, R R

2010-07-01

Complex Regional Pain Syndrome (CRPS) is a neuropathic disease that presents a continuing challenge in terms of pathophysiology, diagnosis, and treatment. Recent studies of neuropathic pain, in both animals and patients, have established a direct relationship between abnormal thalamic rhythmicity related to Thalamo-cortical Dysrhythmia (TCD) and the occurrence of central pain. Here, this relationship has been examined using magneto-encephalographic (MEG) imaging in CRPS Type I, characterized by the absence of nerve lesions. The study addresses spontaneous MEG activity from 13 awake, adult patients (2 men, 11 women; age 15-62), with CRPS Type I of one extremity (duration range: 3months to 10years) and from 13 control subjects. All CRPS I patients demonstrated peaks in power spectrum in the delta (<4Hz) and/or theta (4-9Hz) frequency ranges resulting in a characteristically increased spectral power in those ranges when compared to control subjects. The localization of such abnormal activity, implemented using independent component analysis (ICA) of the sensor data, showed delta and/or theta range activity localized to the somatosensory cortex corresponding to the pain localization, and to orbitofrontal-temporal cortices related to the affective pain perception. Indeed, CRPS Type I patients presented abnormal brain activity typical of TCD, which has both diagnostic value indicating a central origin for this ailment and a potential treatment interest involving pharmacological and electrical stimulation therapies. Copyright 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.

Striatal abnormalities in trichotillomania: a multi-site MRI analysis.

PubMed

Isobe, Masanori; Redden, Sarah A; Keuthen, Nancy J; Stein, Dan J; Lochner, Christine; Grant, Jon E; Chamberlain, Samuel R

2018-01-01

Trichotillomania (hair-pulling disorder) is characterized by the repetitive pulling out of one's own hair, and is classified as an Obsessive-Compulsive Related Disorder. Abnormalities of the ventral and dorsal striatum have been implicated in disease models of trichotillomania, based on translational research, but direct evidence is lacking. The aim of this study was to elucidate subcortical morphometric abnormalities, including localized curvature changes, in trichotillomania. De-identified MRI scans were pooled by contacting authors of previous peer-reviewed studies that examined brain structure in adult patients with trichotillomania, following an extensive literature search. Group differences on subcortical volumes of interest were explored (t-tests) and localized differences in subcortical structure morphology were quantified using permutation testing. The pooled sample comprised N=68 individuals with trichotillomania and N=41 healthy controls. Groups were well-matched in terms of age, gender, and educational levels. Significant volumetric reductions were found in trichotillomania patients versus controls in right amygdala and left putamen. Localized shape deformities were found in bilateral nucleus accumbens, bilateral amygdala, right caudate and right putamen. Structural abnormalities of subcortical regions involved in affect regulation, inhibitory control, and habit generation, play a key role in the pathophysiology of trichotillomania. Trichotillomania may constitute a useful model through which to better understand other compulsive symptoms. These findings may account for why certain medications appear effective for trichotillomania, namely those modulating subcortical dopamine and glutamatergic function. Future work should study the state versus trait nature of these changes, and the impact of treatment.

Brain metastatic cancer cells release microRNA-181c-containing extracellular vesicles capable of destructing blood–brain barrier

PubMed Central

Tominaga, Naoomi; Kosaka, Nobuyoshi; Ono, Makiko; Katsuda, Takeshi; Yoshioka, Yusuke; Tamura, Kenji; Lötvall, Jan; Nakagama, Hitoshi; Ochiya, Takahiro

2015-01-01

Brain metastasis is an important cause of mortality in breast cancer patients. A key event during brain metastasis is the migration of cancer cells through blood–brain barrier (BBB). However, the molecular mechanism behind the passage through this natural barrier remains unclear. Here we show that cancer-derived extracellular vesicles (EVs), mediators of cell–cell communication via delivery of proteins and microRNAs (miRNAs), trigger the breakdown of BBB. Importantly, miR-181c promotes the destruction of BBB through the abnormal localization of actin via the downregulation of its target gene, PDPK1. PDPK1 degradation by miR-181c leads to the downregulation of phosphorylated cofilin and the resultant activated cofilin-induced modulation of actin dynamics. Furthermore, we demonstrate that systemic injection of brain metastatic cancer cell-derived EVs promoted brain metastasis of breast cancer cell lines and are preferentially incorporated into the brain in vivo. Taken together, these results indicate a novel mechanism of brain metastasis mediated by EVs that triggers the destruction of BBB. PMID:25828099

Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189

PubMed Central

McAfee, Samuel S.; Guley, Natalie M.; Del Mar, Nobel; Bu, Wei; Heldt, Scott A.; Honig, Marcia G.; Moore, Bob M.

2017-01-01

Abstract Mild traumatic brain injury (mTBI) can cause severe long-term cognitive and emotional deficits, including impaired memory, depression, and persevering fear, but the neuropathological basis of these deficits is uncertain. As medial prefrontal cortex (mPFC) and hippocampus play important roles in memory and emotion, we used multi-site, multi-electrode recordings of oscillatory neuronal activity in local field potentials (LFPs) in awake, head-fixed mice to determine if the functioning of these regions was abnormal after mTBI, using a closed-skull focal cranial blast model. We evaluated mPFC, hippocampus CA1, and primary somatosensory/visual cortical areas (S1/V1). Although mTBI did not alter the power of oscillations, it did cause increased coherence of θ (4-10 Hz) and β (10-30 Hz) oscillations within mPFC and S1/V1, reduced CA1 sharp-wave ripple (SWR)-evoked LFP activity in mPFC, downshifted SWR frequencies in CA1, and enhanced θ-γ phase-amplitude coupling (PAC) within mPFC. These abnormalities might be linked to the impaired memory, depression, and persevering fear seen after mTBI. Treatment with the cannabinoid type-2 (CB2) receptor inverse agonist SMM-189 has been shown to mitigate functional deficits and neuronal injury after mTBI in mice. We found that SMM-189 also reversed most of the observed neurophysiological abnormalities. This neurophysiological rescue is likely to stem from the previously reported reduction in neuron loss and/or the preservation of neuronal function and connectivity resulting from SMM-189 treatment, which appears to stem from the biasing of microglia from the proinflammatory M1 state to the prohealing M2 state by SMM-189. PMID:28828401

Abnormalities in Dynamic Brain Activity Caused by Mild Traumatic Brain Injury Are Partially Rescued by the Cannabinoid Type-2 Receptor Inverse Agonist SMM-189.

PubMed

Liu, Yu; McAfee, Samuel S; Guley, Natalie M; Del Mar, Nobel; Bu, Wei; Heldt, Scott A; Honig, Marcia G; Moore, Bob M; Reiner, Anton; Heck, Detlef H

2017-01-01

Mild traumatic brain injury (mTBI) can cause severe long-term cognitive and emotional deficits, including impaired memory, depression, and persevering fear, but the neuropathological basis of these deficits is uncertain. As medial prefrontal cortex (mPFC) and hippocampus play important roles in memory and emotion, we used multi-site, multi-electrode recordings of oscillatory neuronal activity in local field potentials (LFPs) in awake, head-fixed mice to determine if the functioning of these regions was abnormal after mTBI, using a closed-skull focal cranial blast model. We evaluated mPFC, hippocampus CA1, and primary somatosensory/visual cortical areas (S1/V1). Although mTBI did not alter the power of oscillations, it did cause increased coherence of θ (4-10 Hz) and β (10-30 Hz) oscillations within mPFC and S1/V1, reduced CA1 sharp-wave ripple (SWR)-evoked LFP activity in mPFC, downshifted SWR frequencies in CA1, and enhanced θ-γ phase-amplitude coupling (PAC) within mPFC. These abnormalities might be linked to the impaired memory, depression, and persevering fear seen after mTBI. Treatment with the cannabinoid type-2 (CB2) receptor inverse agonist SMM-189 has been shown to mitigate functional deficits and neuronal injury after mTBI in mice. We found that SMM-189 also reversed most of the observed neurophysiological abnormalities. This neurophysiological rescue is likely to stem from the previously reported reduction in neuron loss and/or the preservation of neuronal function and connectivity resulting from SMM-189 treatment, which appears to stem from the biasing of microglia from the proinflammatory M1 state to the prohealing M2 state by SMM-189.

[Ocular coloboma and results of brain MRI: preliminary results].

PubMed

Denis, D; Girard, N; Levy-Mozziconacci, A; Berbis, J; Matonti, F

2013-03-01

Congenital ocular colobomas are the result of a failure in closure of the embryonal fissure. We present a prospective study (2007-2011) in which we report brain MRI findings in children with ocular coloboma. Thirty-five children (54 eyes) were included; 15 boys, 20 girls with a median age of 24.0 months (1.0-96.0) at first presentation. Within 2 to 3 months following complete ophthalmologic examination, brain MRI was performed. Colobomas were bilateral in 19 cases and unilateral in 16 cases. Eleven different types of coloboma were identified. Of 54 eyes, 74% demonstrated optic nerve coloboma, of which 28 were severe. Of 35 MRI's performed, abnormalities were present in 86%: gyration abnormalities (n=21), lateral ventricular dilatation (n=17), dilatation of the Virchow-Robin and subarachnoid spaces (n=14), signal abnormalities and brain stem malformations (n=14), white matter signal abnormalities (n=11), corpus callosum abnormalities (n=10). Most of these abnormalities were related. Gyration abnormalities were the most frequent. There was no significant association between the severity of the coloboma and the abnormalities found (P=1.0). Likewise, there was no significant association of gyration abnormalities with the severity of coloboma in children (P=1.0). This study shows, for the first time, the existence of frequent cerebral abnormalities on MRI in children with ocular coloboma. The most common abnormality being gyration abnormalities, in 60% of cases. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

Recurrent De Novo Mutations Disturbing the GTP/GDP Binding Pocket of RAB11B Cause Intellectual Disability and a Distinctive Brain Phenotype.

PubMed

Lamers, Ideke J C; Reijnders, Margot R F; Venselaar, Hanka; Kraus, Alison; Jansen, Sandra; de Vries, Bert B A; Houge, Gunnar; Gradek, Gyri Aasland; Seo, Jieun; Choi, Murim; Chae, Jong-Hee; van der Burgt, Ineke; Pfundt, Rolph; Letteboer, Stef J F; van Beersum, Sylvia E C; Dusseljee, Simone; Brunner, Han G; Doherty, Dan; Kleefstra, Tjitske; Roepman, Ronald

2017-11-02

The Rab GTPase family comprises ∼70 GTP-binding proteins, functioning in vesicle formation, transport and fusion. They are activated by a conformational change induced by GTP-binding, allowing interactions with downstream effectors. Here, we report five individuals with two recurrent de novo missense mutations in RAB11B; c.64G>A; p.Val22Met in three individuals and c.202G>A; p.Ala68Thr in two individuals. An overlapping neurodevelopmental phenotype, including severe intellectual disability with absent speech, epilepsy, and hypotonia was observed in all affected individuals. Additionally, visual problems, musculoskeletal abnormalities, and microcephaly were present in the majority of cases. Re-evaluation of brain MRI images of four individuals showed a shared distinct brain phenotype, consisting of abnormal white matter (severely decreased volume and abnormal signal), thin corpus callosum, cerebellar vermis hypoplasia, optic nerve hypoplasia and mild ventriculomegaly. To compare the effects of both variants with known inactive GDP- and active GTP-bound RAB11B mutants, we modeled the variants on the three-dimensional protein structure and performed subcellular localization studies. We predicted that both variants alter the GTP/GDP binding pocket and show that they both have localization patterns similar to inactive RAB11B. Evaluation of their influence on the affinity of RAB11B to a series of binary interactors, both effectors and guanine nucleotide exchange factors (GEFs), showed induction of RAB11B binding to the GEF SH3BP5, again similar to inactive RAB11B. In conclusion, we report two recurrent dominant mutations in RAB11B leading to a neurodevelopmental syndrome, likely caused by altered GDP/GTP binding that inactivate the protein and induce GEF binding and protein mislocalization. Copyright © 2017 American Society of Human Genetics. All rights reserved.

Fetal magnetic resonance imaging (MRI): a tool for a better understanding of normal and abnormal brain development.

PubMed

Saleem, Sahar N

2013-07-01

Knowledge of the anatomy of the developing fetal brain is essential to detect abnormalities and understand their pathogenesis. Capability of magnetic resonance imaging (MRI) to visualize the brain in utero and to differentiate between its various tissues makes fetal MRI a potential diagnostic and research tool for the developing brain. This article provides an approach to understand the normal and abnormal brain development through schematic interpretation of fetal brain MR images. MRI is a potential screening tool in the second trimester of pregnancies in fetuses at risk for brain anomalies and helps in describing new brain syndromes with in utero presentation. Accurate interpretation of fetal MRI can provide valuable information that helps genetic counseling, facilitates management decisions, and guides therapy. Fetal MRI can help in better understanding the pathogenesis of fetal brain malformations and can support research that could lead to disease-specific interventions.

Brain ultrasound findings in neonates treated with intrauterine transfusion for fetal anaemia.

PubMed

Leijser, Lara M; Vos, Nikki; Walther, Frans J; van Wezel-Meijler, Gerda

2012-09-01

The main causes of severe fetal anaemia are red-cell allo-immunization, parvo B19 virus infection and feto-maternal haemorrhage. Treatment consists of intrauterine transfusion (IUT). Neuro-imaging studies in surviving neonates treated with IUT are scarce. To assess if neonates treated with IUT for fetal anaemia are at risk for cerebral injury, report the incidence and severity of brain ultrasound (US) abnormalities and explore the relation between brain US findings and perinatal parameters and neurological outcome. Brain US scans of neonates born alive between 2001 and 2008 with at least one IUT were retrospectively reviewed and classified as normal, mildly or moderately/severely abnormal. Incidences of abnormalities were calculated for full-term and preterm neonates. Presence and severity of abnormalities were related to clinical and IUT related parameters and to neurological outcome around 2 years of age (adverse: moderate or severe disability; favourable: normal or mild disability). A total of 127 neonates (82 born preterm) were included. Median number of IUTs was 3 (range 1-6) and of brain US 2 (1-6). Median gestational age and weight at birth were 36.6 (26.0-41.1) weeks and 2870 (1040-3950)g. In 72/127 (57%) neonates ≥1 abnormality was seen on brain US, classified as moderate/severe in 30/127 (24%). Neurological outcome was adverse in 5 infants. Presence of brain US abnormalities was not significantly related to any of the perinatal parameters or to neurological outcome. Neonates undergoing IUT for fetal anaemia are at high risk of brain injury. Copyright © 2012 Elsevier Ltd. All rights reserved.

Machine learning based brain tumour segmentation on limited data using local texture and abnormality.

PubMed

Bonte, Stijn; Goethals, Ingeborg; Van Holen, Roel

2018-05-07

Brain tumour segmentation in medical images is a very challenging task due to the large variety in tumour shape, position, appearance, scanning modalities and scanning parameters. Most existing segmentation algorithms use information from four different MRI-sequences, but since this is often not available, there is need for a method able to delineate the different tumour tissues based on a minimal amount of data. We present a novel approach using a Random Forests model combining voxelwise texture and abnormality features on a contrast-enhanced T1 and FLAIR MRI. We transform the two scans into 275 feature maps. A random forest model next calculates the probability to belong to 4 tumour classes or 5 normal classes. Afterwards, a dedicated voxel clustering algorithm provides the final tumour segmentation. We trained our method on the BraTS 2013 database and validated it on the larger BraTS 2017 dataset. We achieve median Dice scores of 40.9% (low-grade glioma) and 75.0% (high-grade glioma) to delineate the active tumour, and 68.4%/80.1% for the total abnormal region including edema. Our fully automated brain tumour segmentation algorithm is able to delineate contrast enhancing tissue and oedema with high accuracy based only on post-contrast T1-weighted and FLAIR MRI, whereas for non-enhancing tumour tissue and necrosis only moderate results are obtained. This makes the method especially suitable for high-grade glioma. Copyright © 2018 Elsevier Ltd. All rights reserved.

Serial computed tomography and magnetic resonance imaging findings of biphasic acute hemorrhagic leukoencephalitis localized to the brain stem and cerebellum.

PubMed

Lee, Nyoung Keun; Lee, Byung Hoon; Hwang, Yoon Joon; Kim, Su Young; Lee, Ji Young; Joo, Mee

2011-04-01

Acute hemorrhagic leukoencephalitis (AHL) is a rare and usually fatal disease characterized by an acute onset of neurological abnormalities. We describe the case of a 37-year-old man with biphasic AHL with a focus on the rare involvement of the brain stem and cerebellum. Initial computed tomography (CT) and magnetic resonance imaging revealed two hemorrhagic foci in the left middle cerebellar peduncle. After 15 days multifocal hematomas in the contralateral cerebellar hemisphere were imaged using CT. The pathological diagnosis was AHL. Following high-dose steroid treatment, the patient recovered with minor neurological sequelae.

Infantile Autism and Computerized Tomography Brain-Scan Findings: Specific versus Nonspecific Abnormalities.

ERIC Educational Resources Information Center

Balottin, Umberto; And Others

1989-01-01

The study of computerized tomography brain-scan findings with 45 autistic and 19 control subjects concluded that autism is nonspecifically associated with brain-scan abnormalities, and that other nonorganic, as well as organic, factors should be taken into account. (Author/DB)

Rapid Morphological Brain Abnormalities during Acute Methamphetamine Intoxication in the Rat. An Experimental study using Light and Electron Microscopy

PubMed Central

Sharma, Hari S.; Kiyatkin, Eugene A.

2009-01-01

This study describes morphological abnormalities of brain cells during acute methamphetamine (METH) intoxication in the rat and demonstrates the role of hyperthermia, disruption of the blood-brain barrier (BBB) and edema in their development. Rats with chronically implanted brain, muscle and skin temperature probes and an intravenous (iv) catheter were exposed to METH (9 mg/kg) at standard (23°C) and warm (29°C) ambient temperatures, allowing for the observation of hyperthermia ranging from mild to pathological levels (38–42°C). When brain temperature peaked or reached a level suggestive of possible lethality (>41.5°C), rats were injected with Evans blue (EB), rapidly anesthetized, perfused, and their brains were taken for further analyses. Four brain areas (cortex, hippocampus, thalamus and hypothalamus) were analyzed for EB extravasation, water and electrolyte (Na+, K+, Cl−) contents, immunostained for albumin and glial fibrillary acidic protein, and examined for neuronal, glial and axonal alterations using standard light and electron microscopy. These examinations revealed profound abnormalities in neuronal, glial, and endothelial cells, which were stronger with METH administered at 29°C than 23°C and tightly correlated with brain and body hyperthermia. These changes had some structural specificity, but in each structure they tightly correlated with increases in EB levels, the numbers of albumin-positive cells, and water and ion contents, suggesting leakage of the BBB, acutely developing brain edema, and serious shifts in brain ion homeostasis as leading factors underlying brain abnormalities. While most of these acute structural and functional abnormalities appear to be reversible, they could trigger subsequent cellular alterations in the brain and accelerate neurodegeneration—the most dangerous complication of chronic amphetamine-like drug abuse. PMID:18773954

Preliminary evidence for obesity and elevations in fasting insulin mediating associations between cortisol awakening response and hippocampal volumes and frontal atrophy.

PubMed

Ursache, Alexandra; Wedin, William; Tirsi, Aziz; Convit, Antonio

2012-08-01

Recent studies have demonstrated alterations in the cortisol awakening response (CAR) and brain abnormalities in adults with obesity and type 2 diabetes mellitus (T2DM). While adolescents with T2DM exhibit similar brain abnormalities, less is known about whether brain impairments and hypothalamic-pituitary-adrenal (HPA) axis abnormalities are already present in adolescents with pre-diabetic conditions such as insulin resistance (IR). This study included 33 adolescents with IR and 20 without IR. Adolescents with IR had a blunted CAR, smaller hippocampal volumes, and greater frontal lobe atrophy compared to controls. Mediation analyses indicated pathways whereby a smaller CAR was associated with higher BMI which was in turn associated with fasting insulin levels, which in turn was related to smaller hippocampal volume and greater frontal lobe atrophy. While we had hypothesized that HPA dysregulation may result from brain abnormalities, our findings suggest that HPA dysregulation may also impact brain structures through associations with metabolic abnormalities. Copyright © 2012 Elsevier Ltd. All rights reserved.

Frequency of brain MRI abnormalities in neuromyelitis optica spectrum disorder at presentation: A cohort of Latin American patients.

PubMed

Carnero Contentti, Edgar; Daccach Marques, Vanessa; Soto de Castillo, Ibis; Tkachuk, Veronica; Antunes Barreira, Amilton; Armas, Elizabeth; Chiganer, Edson; de Aquino Cruz, Camila; Di Pace, José Luis; Hryb, Javier Pablo; Lavigne Moreira, Carolina; Lessa, Carmen; Molina, Omaira; Perassolo, Monica; Soto, Arnoldo; Caride, Alejandro

2018-01-01

Brain magnetic resonance imaging (BMRI) lesions were classically not reported in neuromyelitis optica (NMO). However, BMRI lesions are not uncommon in NMO spectrum disorder (NMOSD) patients. To report BMRI characteristic abnormalities (location and configuration) in NMOSD patients at presentation. Medical records and BMRI characteristics of 79 patients with NMOSD (during the first documented attack) in Argentina, Brazil and Venezuela were reviewed retrospectively. BMRI abnormalities were observed in 81.02% of NMOSD patients at presentation. Forty-two patients (53.1%) showed typical-NMOSD abnormalities. We found BMRI abnormalities at presentation in the brainstem/cerebellum (n = 26; 32.9%), optic chiasm (n = 16; 20.2%), area postrema (n = 13; 16.4%), thalamus/hypothalamus (n = 11; 13.9%), corpus callosum (n = 11; 13.9%), periependymal-third ventricle (n = 9; 11.3%), corticospinal tract (n = 7; 8.8%), hemispheric white matter (n = 1; 1.2%) and nonspecific areas (n = 49; 62.03%). Asymptomatic BMRI lesions were more common. The frequency of brain MRI abnormalities did not differ between patients who were positive and negative for aquaporin 4 antibodies at presentation. Typical brain MRI abnormalities are frequent in NMOSD at disease onset. Copyright © 2017 Elsevier B.V. All rights reserved.

Cortical thickness and folding deficits in conduct-disordered adolescents

PubMed Central

Hyatt, Christopher J.; Haney-Caron, Emily; Stevens, Michael C.

2012-01-01

Background Studies of pediatric conduct disorder (CD) have described frontal and temporal lobe structural abnormalities that parallel findings in antisocial adults. The purpose of this study was to examine previously unexplored cortical thickness and folding as markers for brain abnormalities in “pure CD”-diagnosed adolescents. Based on current fronto-temporal theories, we hypothesized that CD youth would have thinner cortex or less cortical folding in temporal and frontal lobes than control subjects. Methods We obtained T1-weighted brain structure images from n=24 control and n=19 CD participants aged 12–18 years, matched by overall gender and age. We measured group differences in cortical thickness and local gyrification index (regional cortical folding measure) using surface-based morphometry with clusterwise correction for multiple comparisons. Results CD participants, when compared with controls, showed both reduced cortical thickness and folding. Thinner cortex was located primarily in posterior brain regions, including left superior temporal and parietal lobes, temporoparietal junction and paracentral lobule, right superior temporal and parietal lobes, temporoparietal junction and precuneus. Folding deficits were located mainly in anterior brain regions and included left insula, ventro- and dorsomedial prefrontal, anterior cingulate and orbitofrontal cortices, temporal lobe, right superior frontal and parietal lobes and paracentral lobule. Conclusions Our findings generally agree with previous CD volumetric studies, but here show the unique contributions of cortical thickness and folding to gray matter reductions in pure CD in different brain regions. PMID:22209639

Reduced hemispheric asymmetry of brain anatomical networks in attention deficit hyperactivity disorder.

PubMed

Li, Dandan; Li, Ting; Niu, Yan; Xiang, Jie; Cao, Rui; Liu, Bo; Zhang, Hui; Wang, Bin

2018-05-11

Despite many studies reporting a variety of alterations in brain networks in patients with attention deficit hyperactivity disorder (ADHD), alterations in hemispheric anatomical networks are still unclear. In this study, we investigated topology alterations in hemispheric white matter in patients with ADHD and the relationship between these alterations and clinical features of the illness. Weighted hemispheric brain anatomical networks were first constructed for each of 40 right-handed patients with ADHD and 53 matched normal controls. Then, graph theoretical approaches were utilized to compute hemispheric topological properties. The small-world property was preserved in the hemispheric network. Furthermore, a significant group-by-hemisphere interaction was revealed in global efficiency, local efficiency and characteristic path length, attributed to the significantly reduced hemispheric asymmetry of global and local integration in patients with ADHD compared with normal controls. Specifically, reduced asymmetric regional efficiency was found in three regions. Finally, we found that the abnormal asymmetry of hemispheric brain anatomical network topology and regional efficiency were both associated with clinical features (the Adult ADHD Self-Report Scale and Wechsler Adult Intelligence Scale) in patients. Our findings provide new insights into the lateralized nature of hemispheric dysconnectivity and highlight the potential for using brain network measures of hemispheric asymmetry as neural biomarkers for ADHD and its clinical features.

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum

PubMed Central

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R.; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-01-01

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain. PMID:25871402

Experimental microembolism induces localized neuritic pathology in guinea pig cerebrum.

PubMed

Li, Jian-Ming; Cai, Yan; Liu, Fei; Yang, La; Hu, Xia; Patrylo, Peter R; Cai, Huaibin; Luo, Xue-Gang; Xiao, Dong; Yan, Xiao-Xin

2015-05-10

Microbleeds are a common finding in aged human brains. In Alzheimer's disease (AD), neuritic plaques composed of β-amyloid (Aβ) deposits and dystrophic neurites occur frequently around cerebral vasculature, raising a compelling question as to whether, and if so, how, microvascular abnormality and amyloid/neuritic pathology might be causally related. Here we used a guinea pig model of cerebral microembolism to explore a potential inductive effect of vascular injury on neuritic and amyloid pathogenesis. Brains were examined 7-30 days after experimental microvascular embolization occupying ~0.5% of total cortical area. Compared to sham-operated controls, glial fibrillary acidic protein immunoreactivity was increased in the embolized cerebrum, evidently around intracortical vasculature. Swollen/sprouting neurites exhibiting increased reactivity of nicotinamide adenine dinucleotide phosphate diaphorase, parvalbumin, vesicular glutamate transporter 1 and choline acetyltransferase appeared locally in the embolized brains in proximity to intracortical vasculature. The embolization-induced swollen/sprouting neurites were also robustly immunoreactive for β-amyloid precursor protein and β-secretase-1, the substrate and initiating enzyme for Aβ genesis. These experimental data suggest that microvascular injury can induce multisystem neuritic pathology associated with an enhanced amyloidogenic potential in wild-type mammalian brain.

Utility of brain MRI in children with sleep-disordered breathing.

PubMed

Selvadurai, Sarah; Al-Saleh, Suhail; Amin, Reshma; Zweerink, Allison; Drake, James; Propst, Evan J; Narang, Indra

2017-02-01

To investigate the utility of a brain magnetic resonance imaging (MRI) in children with sleep-disordered breathing (SDB), classified as isolated obstructive sleep apnea (OSA) in the absence of adenotonsillar hypertrophy, persistent OSA following adenotonsillectomy, isolated central sleep apnea (CSA) of unclear etiology, OSA with coexisting CSA of unclear etiology, or unexplained nocturnal hypoventilation (NH). Retrospective chart review of polysomnography (PSG) and brain MRI data. Children with PSG evidence of SDB, as described above, and who subsequently had their first brain MRI, were included. PSG, MRI data, and subsequent interventions were recorded. A total of 59 of 6,087 (1%) children met inclusion criteria. Of those, 28 of 59 (47%) were nonsyndromic children and 31 of 59 (53%) were syndromic children with an underlying medical disorder. Abnormal brain MRI findings were observed in 19 of 59 (32%) children, where eight of 19 (42%) were nonsyndromic and 11 of 19 (58%) were syndromic. Abnormal brain MRI findings were most common in syndromic children with combined OSA and CSA without adenotonsillar hypertrophy. Isolated OSA was also a common PSG finding associated with an abnormal brain MRI. Of the nonsyndromic children with an abnormal brain MRI, the most common abnormal brain MRI finding was Chiari malformation (CM), observed in 88% of the group. A brainstem tumor was identified in one nonsyndromic child. Interventions following brain MRI included neurosurgery, chemotherapy, and noninvasive positive pressure ventilation (NiPPV). A brain MRI is an important diagnostic tool in syndromic and nonsyndromic children, especially in children with either isolated OSA or combined OSA and CSA without a clear etiology. 4. Laryngoscope, 2016 127:513-519, 2017. © 2016 The American Laryngological, Rhinological and Otological Society, Inc.

Functional Brain Network Abnormalities during Verbal Working Memory Performance in Adolescents and Young Adults with Dyslexia

ERIC Educational Resources Information Center

Wolf, Robert Christian; Sambataro, Fabio; Lohr, Christina; Steinbrink, Claudia; Martin, Claudia; Vasic, Nenad

2010-01-01

Behavioral and functional neuroimaging studies indicate deficits in verbal working memory (WM) and frontoparietal dysfunction in individuals with dyslexia. Additionally, structural brain abnormalities in dyslexics suggest a dysconnectivity of brain regions associated with phonological processing. However, little is known about the functional…

78 FR 734 - Medical Imaging Drugs Advisory Committee; Notice of Meeting

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-04

..., LLC. The proposed indication (use) for this product is for magnetic resonance imaging in brain...) to detect and visualize areas with disruption of the blood brain barrier (specialized tissues that help protect the brain) and/or abnormal vascularity (abnormal blood circulation). FDA intends to make...

Mid-gestation brain Doppler and head biometry in fetuses with congenital heart disease predict abnormal brain development at birth.

PubMed

Masoller, N; Sanz-CortéS, M; Crispi, F; Gómez, O; Bennasar, M; Egaña-Ugrinovic, G; Bargalló, N; Martínez, J M; Gratacós, E

2016-01-01

Fetuses with congenital heart disease (CHD) show evidence of abnormal brain development before birth, which is thought to contribute to adverse neurodevelopment during childhood. Our aim was to evaluate whether brain development in late pregnancy can be predicted by fetal brain Doppler, head biometry and the clinical form of CHD at the time of diagnosis. This was a prospective cohort study including 58 fetuses with CHD, diagnosed at 20-24 weeks' gestation, and 58 normal control fetuses. At the time of diagnosis, we recorded fetal head circumference (HC), biparietal diameter, middle cerebral artery pulsatility index (MCA-PI), cerebroplacental ratio (CPR) and brain perfusion by fractional moving blood volume. We classified cases into one of two clinical types defined by the expected levels (high or low) of placental (well-oxygenated) blood perfusion, according to the anatomical defect. All fetuses underwent subsequent 3T-magnetic resonance imaging (MRI) at 36-38 weeks' gestation. Abnormal prenatal brain development was defined by a composite score including any of the following findings on MRI: total brain volume <  10(th) centile, parietoccipital or cingulate fissure depth <  10(th) centile or abnormal metabolic profile in the frontal lobe. Logistic regression analysis demonstrated that MCA-PI (odds ratio (OR), 12.7; P = 0.01), CPR (OR, 8.7; P = 0.02) and HC (OR, 6.2; P = 0.02) were independent predictors of abnormal neurodevelopment; however, the clinical type of CHD was not. Fetal brain Doppler and head biometry at the time of CHD diagnosis are independent predictors of abnormal brain development at birth, and could be used in future algorithms to improve counseling and targeted interventions. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd. Copyright © 2015 ISUOG. Published by John Wiley & Sons Ltd.

Low copper and high manganese levels in prion protein plaques

USGS Publications Warehouse

Johnson, Christopher J.; Gilbert, P.U.P.A.; Abrecth, Mike; Baldwin, Katherine L.; Russell, Robin E.; Pedersen, Joel A.; McKenzie, Debbie

2013-01-01

Accumulation of aggregates rich in an abnormally folded form of the prion protein characterize the neurodegeneration caused by transmissible spongiform encephalopathies (TSEs). The molecular triggers of plaque formation and neurodegeneration remain unknown, but analyses of TSE-infected brain homogenates and preparations enriched for abnormal prion protein suggest that reduced levels of copper and increased levels of manganese are associated with disease. The objectives of this study were to: (1) assess copper and manganese levels in healthy and TSE-infected Syrian hamster brain homogenates; (2) determine if the distribution of these metals can be mapped in TSE-infected brain tissue using X-ray photoelectron emission microscopy (X-PEEM) with synchrotron radiation; and (3) use X-PEEM to assess the relative amounts of copper and manganese in prion plaques in situ. In agreement with studies of other TSEs and species, we found reduced brain levels of copper and increased levels of manganese associated with disease in our hamster model. We also found that the in situ levels of these metals in brainstem were sufficient to image by X-PEEM. Using immunolabeled prion plaques in directly adjacent tissue sections to identify regions to image by X-PEEM, we found a statistically significant relationship of copper-manganese dysregulation in prion plaques: copper was depleted whereas manganese was enriched. These data provide evidence for prion plaques altering local transition metal distribution in the TSE-infected central nervous system.

Abnormal small-world architecture of top–down control networks in obsessive–compulsive disorder

PubMed Central

Zhang, Tijiang; Wang, Jinhui; Yang, Yanchun; Wu, Qizhu; Li, Bin; Chen, Long; Yue, Qiang; Tang, Hehan; Yan, Chaogan; Lui, Su; Huang, Xiaoqi; Chan, Raymond C.K.; Zang, Yufeng; He, Yong; Gong, Qiyong

2011-01-01

Background Obsessive–compulsive disorder (OCD) is a common neuropsychiatric disorder that is characterized by recurrent intrusive thoughts, ideas or images and repetitive ritualistic behaviours. Although focal structural and functional abnormalities in specific brain regions have been widely studied in populations with OCD, changes in the functional relations among them remain poorly understood. This study examined OCD–related alterations in functional connectivity patterns in the brain’s top–down control network. Methods We applied resting-state functional magnetic resonance imaging to investigate the correlation patterns of intrinsic or spontaneous blood oxygen level–dependent signal fluctuations in 18 patients with OCD and 16 healthy controls. The brain control networks were first constructed by thresholding temporal correlation matrices of 39 brain regions associated with top–down control and then analyzed using graph theory-based approaches. Results Compared with healthy controls, the patients with OCD showed decreased functional connectivity in the posterior temporal regions and increased connectivity in various control regions such as the cingulate, precuneus, thalamus and cerebellum. Furthermore, the brain’s control networks in the healthy controls showed small-world architecture (high clustering coefficients and short path lengths), suggesting an optimal balance between modularized and distributed information processing. In contrast, the patients with OCD showed significantly higher local clustering, implying abnormal functional organization in the control network. Further analysis revealed that the changes in network properties occurred in regions of increased functional connectivity strength in patients with OCD. Limitations The patient group in the present study was heterogeneous in terms of symptom clusters, and most of the patients with OCD were medicated. Conclusion Our preliminary results suggest that the organizational patterns of intrinsic brain activity in the control networks are altered in patients with OCD and thus provide empirical evidence for aberrant functional connectivity in the large-scale brain systems in people with this disorder. PMID:20964957

Cortical thickness as a contributor to abnormal oscillations in schizophrenia?

PubMed

Edgar, J Christopher; Chen, Yu-Han; Lanza, Matthew; Howell, Breannan; Chow, Vivian Y; Heiken, Kory; Liu, Song; Wootton, Cassandra; Hunter, Michael A; Huang, Mingxiong; Miller, Gregory A; Cañive, José M

2014-01-01

Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function-structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time-frequency group differences and associations with STG structure and age were also examined. Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function-structure relationships observed in controls.

Reversible brain atrophy and cognitive impairment in an adolescent Japanese patient with primary adrenal Cushing's syndrome.

PubMed

Ohara, Nobumasa; Suzuki, Hiroshi; Suzuki, Akiko; Kaneko, Masanori; Ishizawa, Masahiro; Furukawa, Kazuo; Abe, Takahiro; Matsubayashi, Yasuhiro; Yamada, Takaho; Hanyu, Osamu; Shimohata, Takayoshi; Sone, Hirohito

2014-01-01

Endogenous Cushing's syndrome is an endocrine disease resulting from chronic exposure to excessive glucocorticoids produced in the adrenal cortex. Although the ultimate outcome remains uncertain, functional and morphological brain changes are not uncommon in patients with this syndrome, and generally persist even after resolution of hypercortisolemia. We present an adolescent patient with Cushing's syndrome who exhibited cognitive impairment with brain atrophy. A 19-year-old Japanese male visited a local hospital following 5 days of behavioral abnormalities, such as money wasting or nighttime wandering. He had hypertension and a 1-year history of a rounded face. Magnetic resonance imaging (MRI) revealed apparently diffuse brain atrophy. Because of high random plasma cortisol levels (28.7 μg/dL) at 10 AM, he was referred to our hospital in August 2011. Endocrinological testing showed adrenocorticotropic hormone-independent hypercortisolemia, and abdominal computed tomography demonstrated a 2.7 cm tumor in the left adrenal gland. The patient underwent left adrenalectomy in September 2011, and the diagnosis of cortisol-secreting adenoma was confirmed histologically. His hypertension and Cushingoid features regressed. Behavioral abnormalities were no longer observed, and he was classified as cured of his cognitive disturbance caused by Cushing's syndrome in February 2012. MRI performed 8 months after surgery revealed reversal of brain atrophy, and his subsequent course has been uneventful. In summary, the young age at onset and the short duration of Cushing's syndrome probably contributed to the rapid recovery of both cognitive dysfunction and brain atrophy in our patient. Cushing's syndrome should be considered as a possible etiological factor in patients with cognitive impairment and brain atrophy that is atypical for their age.

UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures

PubMed Central

Liu, Yidan; Zhang, Bin; Meng, Xiaoyu; Korn, Matthew J.; Parent, Jack M.; Lu, Lin-Yu; Yu, Xiaochun

2017-01-01

ABSTRACT The 5-methylcytosine (5mC) modification regulates multiple cellular processes and is faithfully maintained following DNA replication. In addition to DNA methyltransferase (DNMT) family proteins, ubiquitin-like PHD and ring finger domain-containing protein 1 (UHRF1) plays an important role in the maintenance of 5mC levels. Loss of UHRF1 abolishes 5mC in cells and leads to embryonic lethality in mice. Interestingly, UHRF1 has a paralog, UHRF2, that has similar sequence and domain architecture, but its biologic function is not clear. Here, we have generated Uhrf2 knockout mice and characterized the role of UHRF2 in vivo. Uhrf2 knockout mice are viable, but the adult mice develop frequent spontaneous seizures and display abnormal electrical activities in brain. Despite no global DNA methylation changes, 5mC levels are decreased at certain genomic loci in the brains of Uhrf2 knockout mice. Therefore, our study has revealed a unique role of UHRF2 in the maintenance of local 5mC levels in brain that is distinct from that of its paralog UHRF1. PMID:28402695

Automatic localization of cerebral cortical malformations using fractal analysis.

PubMed

De Luca, A; Arrigoni, F; Romaniello, R; Triulzi, F M; Peruzzo, D; Bertoldo, A

2016-08-21

Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

Automatic localization of cerebral cortical malformations using fractal analysis

NASA Astrophysics Data System (ADS)

De Luca, A.; Arrigoni, F.; Romaniello, R.; Triulzi, F. M.; Peruzzo, D.; Bertoldo, A.

2016-08-01

Malformations of cortical development (MCDs) encompass a variety of brain disorders affecting the normal development and organization of the brain cortex. The relatively low incidence and the extreme heterogeneity of these disorders hamper the application of classical group level approaches for the detection of lesions. Here, we present a geometrical descriptor for a voxel level analysis based on fractal geometry, then define two similarity measures to detect the lesions at single subject level. The pipeline was applied to 15 normal children and nine pediatric patients affected by MCDs following two criteria, maximum accuracy (WACC) and minimization of false positives (FPR), and proved that our lesion detection algorithm is able to detect and locate abnormalities of the brain cortex with high specificity (WACC  =  85%, FPR  =  96%), sensitivity (WACC  =  83%, FPR  =  63%) and accuracy (WACC  =  85%, FPR  =  90%). The combination of global and local features proves to be effective, making the algorithm suitable for the detection of both focal and diffused malformations. Compared to other existing algorithms, this method shows higher accuracy and sensitivity.

[Neurological soft signs in schizophrenia: correlations with age, sex, educational status and psychopathology].

PubMed

Panagiotidis, P; Kaprinis, G; Iacovides, A; Fountoulakis, K

2013-01-01

Though the pathobiology of schizophrenia can be examined in multiple levels, the organic notion of brain disease suggests that neurological features will be present. One straightforward, inexpensive method of investigating brain dysfunction in schizophrenia is thought the bedside assessment of neurological abnormalities with a standard neurological examination. Neurological abnormalities are traditionally classified as "hard signs" (impairments in basic motor, sensory, and reflex behaviors, which do not appear to be affected in schizophrenia) and "soft signs", which refer to more complex phenomena such as abnormalities in motor control, integrative sensory function, sensorimotor integration, and cerebral laterality. Additionally, neurological soft signs (NSS) are minor motor and sensory abnormalities that are considered to be normal in the course of early development but abnormal when elicited in later life or persist beyond childhood. Soft signs also, have no definitive localizing significance but are indicative of subtle brain dysfunction. Most authors believe that they are a reflection not only of deficient integration between the sensory and motor systems, but also of dysfunctional neuronal circuits linking subcortical brain structures such as the basal ganglia, the brain stem, and the limbic system. Throughout the last four decades, studies have consistently shown that NSS are more frequently present in patients with schizophrenia than in normal subjects and non-psychotic psychiatric patients. However, the functional relevance of NSS remains unclear and their specificity has often been challenged, even though there is indication for a relative specificity with regard to diagnosis, or symptomatology. Many studies have considered soft signs as categorical variables thus hampering the evaluation of fluctuation with symptomatology and/or treatment, whereas other studies included insufficient number of assessed signs, or lacked a comprehensive assessment of extrapyramidal symptomatology. Factors such as sex, age or family history of schizophrenia, are said to influence the performance of neurological examination, whereas relative few studies have provided longitudinal follow-up data on neurological soft signs in a sufficient number of patients, in order to address a possible deterioration of neurological functions. Finally, one additional difficulty when analyzing the NSS literature lies in the diversity of symptoms that are evaluated in the studies and/or non-standardized procedures or scoring. We will review some basic issues concerning recurrent difficulties in the measurement and definition of soft signs, as well as controversies on the significance of these signs with respect to clinical subtyping of schizophrenia, and social and demographic variables.

Aberrant Intrinsic Activity and Connectivity in Cognitively Normal Parkinson's Disease.

PubMed

Harrington, Deborah L; Shen, Qian; Castillo, Gabriel N; Filoteo, J Vincent; Litvan, Irene; Takahashi, Colleen; French, Chelsea

2017-01-01

Disturbances in intrinsic activity during resting-state functional MRI (rsfMRI) are common in Parkinson's disease (PD), but have largely been studied in a priori defined subnetworks. The cognitive significance of abnormal intrinsic activity is also poorly understood, as are abnormalities that precede the onset of mild cognitive impairment. To address these limitations, we leveraged three different analytic approaches to identify disturbances in rsfMRI metrics in 31 cognitively normal PD patients (PD-CN) and 30 healthy adults. Subjects were screened for mild cognitive impairment using the Movement Disorders Society Task Force Level II criteria. Whole-brain data-driven analytic approaches first analyzed the amplitude of low-frequency intrinsic fluctuations (ALFF) and regional homogeneity (ReHo), a measure of local connectivity amongst functionally similar regions. We then examined if regional disturbances in these metrics altered functional connectivity with other brain regions. We also investigated if abnormal rsfMRI metrics in PD-CN were related to brain atrophy and executive, visual organization, and episodic memory functioning. The results revealed abnormally increased and decreased ALFF and ReHo in PD-CN patients within the default mode network (posterior cingulate, inferior parietal cortex, parahippocampus, entorhinal cortex), sensorimotor cortex (primary motor, pre/post-central gyrus), basal ganglia (putamen, caudate), and posterior cerebellar lobule VII, which mediates cognition. For default mode network regions, we also observed a compound profile of altered ALFF and ReHo. Most regional disturbances in ALFF and ReHo were associated with strengthened long-range interactions in PD-CN, notably with regions in different networks. Stronger long-range functional connectivity in PD-CN was also partly expanded to connections that were outside the networks of the control group. Abnormally increased activity and functional connectivity appeared to have a pathological, rather than compensatory influence on cognitive abilities tested in this study. Receiver operating curve analyses demonstrated excellent sensitivity (≥90%) of rsfMRI variables in distinguishing patients from controls, but poor accuracy for brain volume and cognitive variables. Altogether these results provide new insights into the topology, cognitive relevance, and sensitivity of aberrant intrinsic activity and connectivity that precedes clinically significant cognitive impairment. Longitudinal studies are needed to determine if these neurocognitive associations presage the development of future mild cognitive impairment or dementia.

Early Brain Vulnerability in Wolfram Syndrome

PubMed Central

Hershey, Tamara; Lugar, Heather M.; Shimony, Joshua S.; Rutlin, Jerrel; Koller, Jonathan M.; Perantie, Dana C.; Paciorkowski, Alex R.; Eisenstein, Sarah A.; Permutt, M. Alan

2012-01-01

Wolfram Syndrome (WFS) is a rare autosomal recessive disease characterized by insulin-dependent diabetes mellitus, optic nerve atrophy, diabetes insipidus, deafness, and neurological dysfunction leading to death in mid-adulthood. WFS is caused by mutations in the WFS1 gene, which lead to endoplasmic reticulum (ER) stress-mediated cell death. Case studies have found widespread brain atrophy in late stage WFS. However, it is not known when in the disease course these brain abnormalities arise, and whether there is differential vulnerability across brain regions and tissue classes. To address this limitation, we quantified regional brain abnormalities across multiple imaging modalities in a cohort of young patients in relatively early stages of WFS. Children and young adults with WFS were evaluated with neurological, cognitive and structural magnetic resonance imaging measures. Compared to normative data, the WFS group had intact cognition, significant anxiety and depression, and gait abnormalities. Compared to healthy and type 1 diabetic control groups, the WFS group had smaller intracranial volume and preferentially affected gray matter volume and white matter microstructural integrity in the brainstem, cerebellum and optic radiations. Abnormalities were detected in even the youngest patients with mildest symptoms, and some measures did not follow the typical age-dependent developmental trajectory. These results establish that WFS is associated with smaller intracranial volume with specific abnormalities in the brainstem and cerebellum, even at the earliest stage of clinical symptoms. This pattern of abnormalities suggests that WFS has a pronounced impact on early brain development in addition to later neurodegenerative effects, representing a significant new insight into the WFS disease process. Longitudinal studies will be critical for confirming and expanding our understanding of the impact of ER stress dysregulation on brain development. PMID:22792385

Brain-derived neurotrophic factor transgenic mice exhibit passive avoidance deficits, increased seizure severity and in vitro hyperexcitability in the hippocampus and entorhinal cortex.

PubMed

Croll, S D; Suri, C; Compton, D L; Simmons, M V; Yancopoulos, G D; Lindsay, R M; Wiegand, S J; Rudge, J S; Scharfman, H E

1999-01-01

Transgenic mice overexpressing brain-derived neurotrophic factor from the beta-actin promoter were tested for behavioral, gross anatomical and physiological abnormalities. Brain-derived neurotrophic factor messenger RNA overexpression was widespread throughout brain. Overexpression declined with age, such that levels of overexpression decreased sharply by nine months. Brain-derived neurotrophic factor transgenic mice had no gross deformities or behavioral abnormalities. However, they showed a significant passive avoidance deficit. This deficit was dependent on continued overexpression, and resolved with age as brain-derived neurotrophic factor transcripts decreased. In addition, the brain-derived neurotrophic factor transgenic mice showed increased seizure severity in response to kainic acid. Hippocampal slices from brain-derived neurotrophic factor transgenic mice showed hyperexcitability in area CA3 and entorhinal cortex, but not in dentate gyrus. Finally, area CA1 long-term potentiation was disrupted, indicating abnormal plasticity. Our data suggest that overexpression of brain-derived neurotrophic factor in the brain can interfere with normal brain function by causing learning impairments and increased excitability. The results also support the hypothesis that excess brain-derived neurotrophic factor could be pro-convulsant in the limbic system.

Brain abnormalities in murderers indicated by positron emission tomography.

PubMed

Raine, A; Buchsbaum, M; LaCasse, L

1997-09-15

Murderers pleading not guilty by reason of insanity (NGRI) are thought to have brain dysfunction, but there have been no previous studies reporting direct measures of both cortical and subcortical brain functioning in this specific group. Positron emission tomography brain imaging using a continuous performance challenge task was conducted on 41 murderers pleading not guilty by reason of insanity and 41 age- and sex-matched controls. Murderers were characterized by reduced glucose metabolism in the prefrontal cortex, superior parietal gyrus, left angular gyrus, and the corpus callosum, while abnormal asymmetries of activity (left hemisphere lower than right) were also found in the amygdala, thalamus, and medial temporal lobe. These preliminary findings provide initial indications of a network of abnormal cortical and subcortical brain processes that may predispose to violence in murderers pleading NGRI.

Modeling the circle of Willis to assess the effect of anatomical variations on the development of unilateral internal carotid artery stenosis.

PubMed

Zhang, Chi; Wang, Ling; Li, Xiaoyun; Li, Shuyu; Pu, Fang; Fan, Yubo; Li, Deyu

2014-01-01

Circle of Willis (CoW) plays a significant role in maintaining the blood supply for the brain. Specifically, when the stenosis occurs in the internal carotid artery (ICA), abnormal structures of CoW would decrease the compensatory capacity, leading to the local insufficiency of cerebral blood supply. The present paper built a series of lumped parameter models for CoW, and simulated the blood redistribution caused by the unilateral ICA stenosis with different severities in cerebral arteries in the normal and abnormal CoW respectively. The results showed that when unilateral ICA stenosis occurred, the collateral circulation was built through the anterior communicating artery and the ipsilateral posterior communicating artery, maintaining the flow in cerebral arteries. The absence of the two communicating arteries would cause an obvious decrease of flow in local cerebral arteries in the anterior circulation. In conclusion, the two arteries play a significant role in maintaining the balance of cerebral blood supply in the development of ICA stenosis.

Immunocytochemical detection of the microsomal glucose-6-phosphatase in human brain astrocytes.

PubMed

Bell, J E; Hume, R; Busuttil, A; Burchell, A

1993-10-01

Using an antibody raised against the catalytic subunit of glucose-6-phosphatase, this enzyme was immunolocalized in many astrocytes in 20 normal human brains. Double immunofluorescence studies showed co-localization of glial fibrillary acidic protein (GFAP) with glucose-6-phosphatase in astrocytes. However, not all GFAP-positive cells were also glucose-6-phosphatase positive, indicating that some astrocytes do not contain demonstrable expression of this enzyme. Reactive astrocytes in a variety of abnormal brains were strongly glucose-6-phosphatase positive, but neoplastic astrocytes were often only weakly positive. Expression of the enzyme could not be demonstrated in radial glia, neurons or oligodendroglia. Astrocytes normally contain glycogen and the demonstration that some astrocytes also contain glucose-6-phosphatase indicates that they are competent for both glycogenolysis and gluconeogenesis, which may be critical for neuronal welfare.

Localization of Asymmetric Brain Function in Emotion and Depression

PubMed Central

Herrington, John D.; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S.; Banich, Marie T.; Webb, Andrew G.; Miller, Gregory A.

2011-01-01

Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used. PMID:20070577

Localization of asymmetric brain function in emotion and depression.

PubMed

Herrington, John D; Heller, Wendy; Mohanty, Aprajita; Engels, Anna S; Banich, Marie T; Webb, Andrew G; Miller, Gregory A

2010-05-01

Although numerous EEG studies have shown that depression is associated with abnormal functional asymmetries in frontal cortex, fMRI and PET studies have largely failed to identify specific brain areas showing this effect. The present study tested the hypothesis that emotion processes are related to asymmetric patterns of fMRI activity, particularly within dorsolateral prefrontal cortex (DLPFC). Eleven depressed and 18 control participants identified the color in which pleasant, neutral, and unpleasant words were printed. Both groups showed a leftward lateralization for pleasant words in DLPFC. In a neighboring DLPFC area, the depression group showed more right-lateralized activation than controls, replicating EEG findings. These data confirm that emotional stimulus processing and trait depression are associated with asymmetric brain functions in distinct subregions of the DLPFC that may go undetected unless appropriate analytic procedures are used.

Multivariate Tensor-based Morphometry on Surfaces: Application to Mapping Ventricular Abnormalities in HIV/AIDS

PubMed Central

Wang, Yalin; Zhang, Jie; Gutman, Boris; Chan, Tony F.; Becker, James T.; Aizenstein, Howard J.; Lopez, Oscar L.; Tamburo, Robert J.; Toga, Arthur W.; Thompson, Paul M.

2010-01-01

Here we developed a new method, called multivariate tensor-based surface morphometry (TBM), and applied it to study lateral ventricular surface differences associated with HIV/AIDS. Using concepts from differential geometry and the theory of differential forms, we created mathematical structures known as holomorphic one-forms, to obtain an efficient and accurate conformal parameterization of the lateral ventricular surfaces in the brain. The new meshing approach also provides a natural way to register anatomical surfaces across subjects, and improves on prior methods as it handles surfaces that branch and join at complex 3D junctions. To analyze anatomical differences, we computed new statistics from the Riemannian surface metrics - these retain multivariate information on local surface geometry. We applied this framework to analyze lateral ventricular surface morphometry in 3D MRI data from 11 subjects with HIV/AIDS and 8 healthy controls. Our method detected a 3D profile of surface abnormalities even in this small sample. Multivariate statistics on the local tensors gave better effect sizes for detecting group differences, relative to other TBM-based methods including analysis of the Jacobian determinant, the largest and smallest eigenvalues of the surface metric, and the pair of eigenvalues of the Jacobian matrix. The resulting analysis pipeline may improve the power of surface-based morphometry studies of the brain. PMID:19900560

Cytoplasmic mislocalization of RNA splicing factors and aberrant neuronal gene splicing in TDP-43 transgenic pig brain.

PubMed

Wang, Guohao; Yang, Huaqiang; Yan, Sen; Wang, Chuan-En; Liu, Xudong; Zhao, Bentian; Ouyang, Zhen; Yin, Peng; Liu, Zhaoming; Zhao, Yu; Liu, Tao; Fan, Nana; Guo, Lin; Li, Shihua; Li, Xiao-Jiang; Lai, Liangxue

2015-09-03

TAR DNA-binding protein 43 (TDP-43) is a nuclear protein, but it is redistributed in the neuronal cytoplasm in both amyotrophic lateral sclerosis (ALS) and frontotemporal lobar degeneration (FTLD). Because small transgenic animal models often lack cytoplasmic TDP-43, how the cytoplasmic accumulation of TDP-43 contributes to these diseases remains unclear. The current study is aimed at studying the mechanism of cytoplasmic pathology of TDP-43. We established transgenic pigs expressing mutant TDP-43 (M337V). This pig model shows severe phenotypes and early death. We found that transgenic TDP-43 is also distributed in the cytoplasm of neuronal cells in the spinal cord and brain. Transgenic TDP-43 interacts with PSF, an RNA splicing factor that associates with NeuN to regulate neuronal RNA splicing. The interaction of TDP-43, PSF and NeuN causes PSF and NeuN mislocalize into the neuronal cytoplasm in transgenic pigs. Consistently, abnormal PSF-related neuronal RNA splicing is seen in TDP-43 transgenic pigs. The cytoplasmic localization of PSF and NeuN as well as abnormal PSF-related neuronal RNA splicing was also found in ALS patient brains. Our findings from a large mammalian model suggest that cytoplasmic mutant TDP-43 could reduce the nuclear function of RNA splicing factors, contributing to neuropathology.

Individualized statistical learning from medical image databases: application to identification of brain lesions.

PubMed

Erus, Guray; Zacharaki, Evangelia I; Davatzikos, Christos

2014-04-01

This paper presents a method for capturing statistical variation of normal imaging phenotypes, with emphasis on brain structure. The method aims to estimate the statistical variation of a normative set of images from healthy individuals, and identify abnormalities as deviations from normality. A direct estimation of the statistical variation of the entire volumetric image is challenged by the high-dimensionality of images relative to smaller sample sizes. To overcome this limitation, we iteratively sample a large number of lower dimensional subspaces that capture image characteristics ranging from fine and localized to coarser and more global. Within each subspace, a "target-specific" feature selection strategy is applied to further reduce the dimensionality, by considering only imaging characteristics present in a test subject's images. Marginal probability density functions of selected features are estimated through PCA models, in conjunction with an "estimability" criterion that limits the dimensionality of estimated probability densities according to available sample size and underlying anatomy variation. A test sample is iteratively projected to the subspaces of these marginals as determined by PCA models, and its trajectory delineates potential abnormalities. The method is applied to segmentation of various brain lesion types, and to simulated data on which superiority of the iterative method over straight PCA is demonstrated. Copyright © 2014 Elsevier B.V. All rights reserved.

The study of autism as a distributed disorder

PubMed Central

Müller, Ralph-Axel

2010-01-01

Past autism research has often been dedicated to tracing the causes of the disorder to a localized neurological abnormality, a single functional network, or a single cognitive-behavioral domain. In this review, I argue that autism is a ‘distributed disorder’ on various levels of study (genetic, neuroanatomical, neurofunctional, behavioral). ‘Localizing’ models are therefore not promising. The large array of potential genetic risk factors suggests that multiple (or all) emerging functional brain networks are affected during early development. This is supported by widespread growth abnormalities throughout the brain. Interactions during development between affected functional networks and atypical experiential effects (associated with atypical behavior) in children with autism further complicate the neurological bases of the disorder, resulting in an ‘exponentially distributed’ profile. Promising approaches to a better characterization of neural endophenotypes in autism are provided by techniques investigating white matter and connectivity, such as MR spectroscopy, diffusion tensor imaging (DTI), and functional connectivity MRI. According to a recent hypothesis, the autistic brain is generally characterized by ‘underconnectivity’. However, not all findings are consistent with this view. The concepts and methodology of functional connectivity need to be refined and results need to be corroborated by anatomical studies (such as DTI tractography) before definitive conclusions can be drawn. PMID:17326118

Individualized Statistical Learning from Medical Image Databases: Application to Identification of Brain Lesions

PubMed Central

Erus, Guray; Zacharaki, Evangelia I.; Davatzikos, Christos

2014-01-01

This paper presents a method for capturing statistical variation of normal imaging phenotypes, with emphasis on brain structure. The method aims to estimate the statistical variation of a normative set of images from healthy individuals, and identify abnormalities as deviations from normality. A direct estimation of the statistical variation of the entire volumetric image is challenged by the high-dimensionality of images relative to smaller sample sizes. To overcome this limitation, we iteratively sample a large number of lower dimensional subspaces that capture image characteristics ranging from fine and localized to coarser and more global. Within each subspace, a “target-specific” feature selection strategy is applied to further reduce the dimensionality, by considering only imaging characteristics present in a test subject’s images. Marginal probability density functions of selected features are estimated through PCA models, in conjunction with an “estimability” criterion that limits the dimensionality of estimated probability densities according to available sample size and underlying anatomy variation. A test sample is iteratively projected to the subspaces of these marginals as determined by PCA models, and its trajectory delineates potential abnormalities. The method is applied to segmentation of various brain lesion types, and to simulated data on which superiority of the iterative method over straight PCA is demonstrated. PMID:24607564

Machine Learning Classification Combining Multiple Features of A Hyper-Network of fMRI Data in Alzheimer's Disease

PubMed Central

Guo, Hao; Zhang, Fan; Chen, Junjie; Xu, Yong; Xiang, Jie

2017-01-01

Exploring functional interactions among various brain regions is helpful for understanding the pathological underpinnings of neurological disorders. Brain networks provide an important representation of those functional interactions, and thus are widely applied in the diagnosis and classification of neurodegenerative diseases. Many mental disorders involve a sharp decline in cognitive ability as a major symptom, which can be caused by abnormal connectivity patterns among several brain regions. However, conventional functional connectivity networks are usually constructed based on pairwise correlations among different brain regions. This approach ignores higher-order relationships, and cannot effectively characterize the high-order interactions of many brain regions working together. Recent neuroscience research suggests that higher-order relationships between brain regions are important for brain network analysis. Hyper-networks have been proposed that can effectively represent the interactions among brain regions. However, this method extracts the local properties of brain regions as features, but ignores the global topology information, which affects the evaluation of network topology and reduces the performance of the classifier. This problem can be compensated by a subgraph feature-based method, but it is not sensitive to change in a single brain region. Considering that both of these feature extraction methods result in the loss of information, we propose a novel machine learning classification method that combines multiple features of a hyper-network based on functional magnetic resonance imaging in Alzheimer's disease. The method combines the brain region features and subgraph features, and then uses a multi-kernel SVM for classification. This retains not only the global topological information, but also the sensitivity to change in a single brain region. To certify the proposed method, 28 normal control subjects and 38 Alzheimer's disease patients were selected to participate in an experiment. The proposed method achieved satisfactory classification accuracy, with an average of 91.60%. The abnormal brain regions included the bilateral precuneus, right parahippocampal gyrus\\hippocampus, right posterior cingulate gyrus, and other regions that are known to be important in Alzheimer's disease. Machine learning classification combining multiple features of a hyper-network of functional magnetic resonance imaging data in Alzheimer's disease obtains better classification performance. PMID:29209156

Arginyltransferase ATE1 is targeted to the neuronal growth cones and regulates neurite outgrowth during brain development.

PubMed

Wang, Junling; Pavlyk, Iuliia; Vedula, Pavan; Sterling, Stephanie; Leu, N Adrian; Dong, Dawei W; Kashina, Anna

2017-10-01

Arginylation is an emerging protein modification mediated by arginyltransferase ATE1, shown to regulate embryogenesis and actin cytoskeleton, however its functions in different physiological systems are not well understood. Here we analyzed the role of ATE1 in brain development and neuronal growth by producing a conditional mouse knockout with Ate1 deletion in the nervous system driven by Nestin promoter (Nes-Ate1 mice). These mice were weaker than wild type, resulting in low postnatal survival rates, and had abnormalities in the brain that suggested defects in neuronal migration. Cultured Ate1 knockout neurons showed a reduction in the neurite outgrowth and the levels of doublecortin and F-actin in the growth cones. In wild type, ATE1 prominently localized to the growth cones, in addition to the cell bodies. Examination of the Ate1 mRNA sequence reveals the existence of putative zipcode-binding sequences involved in mRNA targeting to the cell periphery and local translation at the growth cones. Fluorescence in situ hybridization showed that Ate1 mRNA localized to the tips of the growth cones, likely due to zipcode-mediated targeting, and this localization coincided with spots of localization of arginylated β-actin, which disappeared in the presence of protein synthesis inhibitors. We propose that zipcode-mediated co-targeting of Ate1 and β-actin mRNA leads to localized co-translational arginylation of β-actin that drives the growth cone migration and neurite outgrowth. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder

PubMed Central

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E.; Brammer, Michael; Fletcher, Paul C.; Bullmore, Edward T.; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G. M.; Bailey, A. J.; Baron-Cohen, S.; Bolton, P. F.; Bullmore, E. T.; Carrington, S.; Chakrabarti, B.; Daly, E. M.; Deoni, S. C.; Ecker, C.; Happe, F.; Henty, J.; Jezzard, P.; Johnston, P.; Jones, D. K.; Lai, M. C.; Lombardo, M. V.; Madden, A.; Mullins, D.; Murphy, C. M.; Murphy, D. G.; Pasco, G.; Sadek, S.; Spain, D.; Steward, R.; Suckling, J.; Wheelwright, S.; Williams, S. C.

2013-01-01

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of “cortical separation distances” to assess the global and local intrinsic “wiring costs” of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical “connectivity” in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms. PMID:23878213

Intrinsic gray-matter connectivity of the brain in adults with autism spectrum disorder.

PubMed

Ecker, Christine; Ronan, Lisa; Feng, Yue; Daly, Eileen; Murphy, Clodagh; Ginestet, Cedric E; Brammer, Michael; Fletcher, Paul C; Bullmore, Edward T; Suckling, John; Baron-Cohen, Simon; Williams, Steve; Loth, Eva; Murphy, Declan G M

2013-08-06

Autism spectrum disorders (ASD) are a group of neurodevelopmental conditions that are accompanied by atypical brain connectivity. So far, in vivo evidence for atypical structural brain connectivity in ASD has mainly been based on neuroimaging studies of cortical white matter. However, genetic studies suggest that abnormal connectivity in ASD may also affect neural connections within the cortical gray matter. Such intrinsic gray-matter connections are inherently more difficult to describe in vivo but may be inferred from a variety of surface-based geometric features that can be measured using magnetic resonance imaging. Here, we present a neuroimaging study that examines the intrinsic cortico-cortical connectivity of the brain in ASD using measures of "cortical separation distances" to assess the global and local intrinsic "wiring costs" of the cortex (i.e., estimated length of horizontal connections required to wire the cortex within the cortical sheet). In a sample of 68 adults with ASD and matched controls, we observed significantly reduced intrinsic wiring costs of cortex in ASD, both globally and locally. Differences in global and local wiring cost were predominantly observed in fronto-temporal regions and also significantly predicted the severity of social and repetitive symptoms (respectively). Our study confirms that atypical cortico-cortical "connectivity" in ASD is not restricted to the development of white-matter connections but may also affect the intrinsic gray-matter architecture (and connectivity) within the cortical sheet. Thus, the atypical connectivity of the brain in ASD is complex, affecting both gray and white matter, and forms part of the core neural substrates underlying autistic symptoms.

Ultrastructural characterization of the tau-immunoreactive tubules in the oligodendroglial perikarya and their inner loop processes in progressive supranuclear palsy.

PubMed

Arima, K; Nakamura, M; Sunohara, N; Ogawa, M; Anno, M; Izumiyama, Y; Hirai, S; Ikeda, K

1997-06-01

Coiled bodies and interfascicular threads are conspicuous white matter abnormalities of brains of patients with progressive supranuclear palsy (PSP). Both structures are argyrophilic and immunoreactive for the microtubule-binding protein tau. This report concerns the ultrastructural localization of interfascicular threads and their relationship to coiled bodies in five PSP patients. We showed for the first time that abnormal tubules with a 13- to 15-nm diameter and fuzzy outer contours were the common structures of coiled bodies in the oligodendroglial perikarya and of interfascicular threads. Moreover, the tubules were immunolabeled by anti-tau antibodies. The abnormal tau-positive tubules of interfascicular threads were located in the inner loop of the myelin sheath. Our study further indicated that the thread-like structures in the white matter comprised, at least in part, oligodendroglial processes, and that they were also present in gray matter. We consider that the formation of coiled bodies in the perikarya and of interfascicular threads represents a common cytoskeletal abnormality of the oligodendroglia of PSP patients. Moreover, even though the white matter alterations of PSP resemble those of corticobasal degeneration, there are certain ultrastructural differences in the abnormal oligodendroglial tubules of the two diseases.

Microstructural Abnormalities Were Found in Brain Gray Matter from Patients with Chronic Myofascial Pain

PubMed Central

Xie, Peng; Qin, Bangyong; Song, Ganjun; Zhang, Yi; Cao, Song; Yu, Jin; Wu, Jianjiang; Wang, Jiang; Zhang, Tijiang; Zhang, Xiaoming; Yu, Tian; Zheng, Hong

2016-01-01

Myofascial pain, presented as myofascial trigger points (MTrPs)-related pain, is a common, chronic disease involving skeletal muscle, but its underlying mechanisms have been poorly understood. Previous studies have revealed that chronic pain can induce microstructural abnormalities in the cerebral gray matter. However, it remains unclear whether the brain gray matters of patients with chronic MTrPs-related pain undergo alteration. In this study, we employed the Diffusion Kurtosis Imaging (DKI) technique, which is particularly sensitive to brain microstructural perturbation, to monitor the MTrPs-related microstructural alterations in brain gray matter of patients with chronic pain. Our results revealed that, in comparison with the healthy controls, patients with chronic myofascial pain exhibited microstructural abnormalities in the cerebral gray matter and these lesions were mainly distributed in the limbic system and the brain areas involved in the pain matrix. In addition, we showed that microstructural abnormalities in the right anterior cingulate cortex (ACC) and medial prefrontal cortex (mPFC) had a significant negative correlation with the course of disease and pain intensity. The results of this study demonstrated for the first time that there are microstructural abnormalities in the brain gray matter of patients with MTrPs-related chronic pain. Our findings may provide new insights into the future development of appropriate therapeutic strategies to this disease. PMID:28066193

If the skull fits: magnetic resonance imaging and microcomputed tomography for combined analysis of brain and skull phenotypes in the mouse

PubMed Central

Blank, Marissa C.; Roman, Brian B.; Henkelman, R. Mark; Millen, Kathleen J.

2012-01-01

The mammalian brain and skull develop concurrently in a coordinated manner, consistently producing a brain and skull that fit tightly together. It is common that abnormalities in one are associated with related abnormalities in the other. However, this is not always the case. A complete characterization of the relationship between brain and skull phenotypes is necessary to understand the mechanisms that cause them to be coordinated or divergent and to provide perspective on the potential diagnostic or prognostic significance of brain and skull phenotypes. We demonstrate the combined use of magnetic resonance imaging and microcomputed tomography for analysis of brain and skull phenotypes in the mouse. Co-registration of brain and skull images allows comparison of the relationship between phenotypes in the brain and those in the skull. We observe a close fit between the brain and skull of two genetic mouse models that both show abnormal brain and skull phenotypes. Application of these three-dimensional image analyses in a broader range of mouse mutants will provide a map of the relationships between brain and skull phenotypes generally and allow characterization of patterns of similarities and differences. PMID:22947655

Automatic brain tumor detection in MRI: methodology and statistical validation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Islam, Mohammad A.; Shaik, Jahangheer; Parra, Carlos; Ogg, Robert

2005-04-01

Automated brain tumor segmentation and detection are immensely important in medical diagnostics because it provides information associated to anatomical structures as well as potential abnormal tissue necessary to delineate appropriate surgical planning. In this work, we propose a novel automated brain tumor segmentation technique based on multiresolution texture information that combines fractal Brownian motion (fBm) and wavelet multiresolution analysis. Our wavelet-fractal technique combines the excellent multiresolution localization property of wavelets to texture extraction of fractal. We prove the efficacy of our technique by successfully segmenting pediatric brain MR images (MRIs) from St. Jude Children"s Research Hospital. We use self-organizing map (SOM) as our clustering tool wherein we exploit both pixel intensity and multiresolution texture features to obtain segmented tumor. Our test results show that our technique successfully segments abnormal brain tissues in a set of T1 images. In the next step, we design a classifier using Feed-Forward (FF) neural network to statistically validate the presence of tumor in MRI using both the multiresolution texture and the pixel intensity features. We estimate the corresponding receiver operating curve (ROC) based on the findings of true positive fractions and false positive fractions estimated from our classifier at different threshold values. An ROC, which can be considered as a gold standard to prove the competence of a classifier, is obtained to ascertain the sensitivity and specificity of our classifier. We observe that at threshold 0.4 we achieve true positive value of 1.0 (100%) sacrificing only 0.16 (16%) false positive value for the set of 50 T1 MRI analyzed in this experiment.

Thyroid Hormone Acts Locally to Increase Neurogenesis, Neuronal Differentiation, and Dendritic Arbor Elaboration in the Tadpole Visual System

PubMed Central

Thompson, Christopher K.

2016-01-01

Thyroid hormone (TH) regulates many cellular events underlying perinatal brain development in vertebrates. Whether and how TH regulates brain development when neural circuits are first forming is less clear. Furthermore, although the molecular mechanisms that impose spatiotemporal constraints on TH action in the brain have been described, the effects of local TH signaling are poorly understood. We determined the effects of manipulating TH signaling on development of the optic tectum in stage 46–49 Xenopus laevis tadpoles. Global TH treatment caused large-scale morphological effects in tadpoles, including changes in brain morphology and increased tectal cell proliferation. Either increasing or decreasing endogenous TH signaling in tectum, by combining targeted DIO3 knockdown and methimazole, led to corresponding changes in tectal cell proliferation. Local increases in TH, accomplished by injecting suspensions of tri-iodothyronine (T3) in coconut oil into the midbrain ventricle or into the eye, selectively increased tectal or retinal cell proliferation, respectively. In vivo time-lapse imaging demonstrated that local TH first increased tectal progenitor cell proliferation, expanding the progenitor pool, and subsequently increased neuronal differentiation. Local T3 also dramatically increased dendritic arbor growth in neurons that had already reached a growth plateau. The time-lapse data indicate that the same cells are differentially sensitive to T3 at different time points. Finally, TH increased expression of genes pertaining to proliferation and neuronal differentiation. These experiments indicate that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting cell proliferation and differentiation and by acting on neurons to increase dendritic arbor elaboration. SIGNIFICANCE STATEMENT Thyroid hormone (TH) is a critical regulator of perinatal brain development in vertebrates. Abnormal TH signaling in early pregnancy is associated with significant cognitive deficits in humans; however, it is difficult to probe the function of TH in early brain development in mammals because of the inaccessibility of the fetal brain in the uterine environment and the challenge of disambiguating maternal versus fetal contributions of TH. The external development of tadpoles allows manipulation and direct observation of the molecular and cellular mechanisms underlying TH's effects on brain development in ways not possible in mammals. We find that endogenous TH locally regulates neurogenesis at developmental stages relevant to circuit assembly by affecting neural progenitor cell proliferation and differentiation and by acting on neurons to enhance dendritic arbor elaboration. PMID:27707971

Neonatal Brain Abnormalities and Memory and Learning Outcomes at 7 Years in Children Born Very Preterm

PubMed Central

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term born controls. Neonatal brain abnormalities, and in particular deep grey matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children, especially global, white-matter, grey-matter and cerebellar abnormalities. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function. PMID:23805915

Dissociation of functional and anatomical brain abnormalities in unaffected siblings of schizophrenia patients.

PubMed

Guo, Wenbin; Song, Yan; Liu, Feng; Zhang, Zhikun; Zhang, Jian; Yu, Miaoyu; Liu, Jianrong; Xiao, Changqing; Liu, Guiying; Zhao, Jingping

2015-05-01

Schizophrenia patients and their unaffected siblings share similar brain functional and structural abnormalities. However, no study is engaged to investigate whether and how functional abnormalities are related to structural abnormalities in unaffected siblings. This study was undertaken to examine the association between functional and anatomical abnormalities in unaffected siblings. Forty-six unaffected siblings of schizophrenia patients and 46 age-, sex-, and education-matched healthy controls underwent structural and resting-state functional magnetic resonance imaging scanning. Voxel-based morphometry (VBM), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF) were utilized to analyze imaging data. The VBM analysis showed gray matter volume decreases in the fronto-temporal regions (the left middle temporal gyrus and right inferior frontal gyrus, orbital part) and increases in basal ganglia system (the left putamen). Functional abnormalities measured by ALFF and fALFF mainly involved in the fronto-limbic-sensorimotor circuit (decreased ALFF in bilateral middle frontal gyrus and the right middle cingulate gyrus, and decreased fALFF in the right inferior frontal gyrus, orbital part; and increased ALFF in the left fusiform gyrus and left lingual gyrus, and increased fALFF in bilateral calcarine cortex). No significant correlation was found between functional and anatomical abnormalities in the sibling group. A dissociation pattern of brain regions with functional and anatomical abnormalities is observed in unaffected siblings. Our findings suggest that brain functional and anatomical abnormalities might be present independently in unaffected siblings of schizophrenia patients. Copyright © 2014 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Neonatal brain abnormalities and memory and learning outcomes at 7 years in children born very preterm.

PubMed

Omizzolo, Cristina; Scratch, Shannon E; Stargatt, Robyn; Kidokoro, Hiroyuki; Thompson, Deanne K; Lee, Katherine J; Cheong, Jeanie; Neil, Jeffrey; Inder, Terrie E; Doyle, Lex W; Anderson, Peter J

2014-01-01

Using prospective longitudinal data from 198 very preterm and 70 full term children, this study characterised the memory and learning abilities of very preterm children at 7 years of age in both verbal and visual domains. The relationship between the extent of brain abnormalities on neonatal magnetic resonance imaging (MRI) and memory and learning outcomes at 7 years of age in very preterm children was also investigated. Neonatal MRI scans were qualitatively assessed for global, white-matter, cortical grey-matter, deep grey-matter, and cerebellar abnormalities. Very preterm children performed less well on measures of immediate memory, working memory, long-term memory, and learning compared with term-born controls. Neonatal brain abnormalities, and in particular deep grey-matter abnormality, were associated with poorer memory and learning performance at 7 years in very preterm children. Findings support the importance of cerebral neonatal pathology for predicting later memory and learning function.

Whole-brain spectroscopic MRI biomarkers identify infiltrating margins in glioblastoma patients

PubMed Central

Cordova, James S.; Shu, Hui-Kuo G.; Liang, Zhongxing; Gurbani, Saumya S.; Cooper, Lee A. D.; Holder, Chad A.; Olson, Jeffrey J.; Kairdolf, Brad; Schreibmann, Eduard; Neill, Stewart G.; Hadjipanayis, Constantinos G.; Shim, Hyunsuk

2016-01-01

Background The standard of care for glioblastoma (GBM) is maximal safe resection followed by radiation therapy with chemotherapy. Currently, contrast-enhanced MRI is used to define primary treatment volumes for surgery and radiation therapy. However, enhancement does not identify the tumor entirely, resulting in limited local control. Proton spectroscopic MRI (sMRI), a method reporting endogenous metabolism, may better define the tumor margin. Here, we develop a whole-brain sMRI pipeline and validate sMRI metrics with quantitative measures of tumor infiltration. Methods Whole-brain sMRI metabolite maps were coregistered with surgical planning MRI and imported into a neuronavigation system to guide tissue sampling in GBM patients receiving 5-aminolevulinic acid fluorescence-guided surgery. Samples were collected from regions with metabolic abnormalities in a biopsy-like fashion before bulk resection. Tissue fluorescence was measured ex vivo using a hand-held spectrometer. Tissue samples were immunostained for Sox2 and analyzed to quantify the density of staining cells using a novel digital pathology image analysis tool. Correlations among sMRI markers, Sox2 density, and ex vivo fluorescence were evaluated. Results Spectroscopic MRI biomarkers exhibit significant correlations with Sox2-positive cell density and ex vivo fluorescence. The choline to N-acetylaspartate ratio showed significant associations with each quantitative marker (Pearson's ρ = 0.82, P < .001 and ρ = 0.36, P < .0001, respectively). Clinically, sMRI metabolic abnormalities predated contrast enhancement at sites of tumor recurrence and exhibited an inverse relationship with progression-free survival. Conclusions As it identifies tumor infiltration and regions at high risk for recurrence, sMRI could complement conventional MRI to improve local control in GBM patients. PMID:26984746

MRI or not to MRI! Should brain MRI be a routine investigation in children with autistic spectrum disorders?

PubMed

Zeglam, Adel M; Al-Ogab, Marwa F; Al-Shaftery, Thouraya

2015-09-01

To evaluate the routine usage of Magnetic Resonance Imaging (MRI) of brain and estimate the prevalence of brain abnormalities in children presenting to the Neurodevelopment Clinic of Al-Khadra Hospital (NDC-KH), Tripoli, Libya with autistic spectrum disorders (ASD). The records of all children with ASD presented to NDC-KH over 4-year period (from January 2009 to December 2012) were reviewed. All MRIs were acquired with a 1.5-T Philips (3-D T1, T2, FLAIR coronal and axial sequences). MRIs were reported to be normal, abnormal or no significant abnormalities by a consultant neuroradiologist. One thousand and seventy-five children were included in the study. Seven hundred and eighty-two children (72.7 %) had an MRI brain of whom 555 (71 %) were boys. 26 children (24 males and 2 females) (3.3 %) demonstrated MRI abnormalities (8 leukodystrophic changes, 4 periventricular leukomalacia, 3 brain atrophy, 2 tuberous sclerosis, 2 vascular changes, 1 pineoblastoma, 1 cerebellar angioma, 1 cerebellar hypoplasia, 3 agenesis of corpus callosum, 1 neuro-epithelial cyst). An unexpectedly high rate of MRI abnormalities was found in the first large series of clinical MRI investigations in children with autism. These results could contribute to further research into the pathogenesis of autistic spectrum disorder.

Partial Tmem106b reduction does not correct abnormalities due to progranulin haploinsufficiency.

PubMed

Arrant, Andrew E; Nicholson, Alexandra M; Zhou, Xiaolai; Rademakers, Rosa; Roberson, Erik D

2018-06-22

Loss of function mutations in progranulin (GRN) are a major cause of frontotemporal dementia (FTD). Progranulin is a secreted glycoprotein that localizes to lysosomes and is critical for proper lysosomal function. Heterozygous GRN mutation carriers develop FTD with TDP-43 pathology and exhibit signs of lysosomal dysfunction in the brain, with increased levels of lysosomal proteins and lipofuscin accumulation. Homozygous GRN mutation carriers develop neuronal ceroid lipofuscinosis (NCL), an earlier-onset lysosomal storage disorder caused by severe lysosomal dysfunction. Multiple genome-wide association studies have shown that risk of FTD in GRN mutation carriers is modified by polymorphisms in TMEM106B, which encodes a lysosomal membrane protein. Risk alleles of TMEM106B may increase TMEM106B levels through a variety of mechanisms. Brains from FTD patients with GRN mutations exhibit increased TMEM106B expression, and protective TMEM106B polymorphisms are associated with decreased TMEM106B expression. Together, these data raise the possibility that reduction of TMEM106B levels may protect against the pathogenic effects of progranulin haploinsufficiency. We crossed Tmem106b +/- mice with Grn +/- mice, which model the progranulin haploinsufficiency of GRN mutation carriers and develop age-dependent social deficits and lysosomal abnormalities in the brain. We tested whether partial Tmem106b reduction could normalize the social deficits and lysosomal abnormalities of Grn +/- mice. Partial reduction of Tmem106b levels did not correct the social deficits of Grn +/- mice. Tmem106b reduction also failed to normalize most lysosomal abnormalities of Grn +/- mice, except for β-glucuronidase activity, which was suppressed by Tmem106b reduction and increased by progranulin insufficiency. These data do not support the hypothesis that Tmem106b reduction protects against the pathogenic effects of progranulin haploinsufficiency, but do show that Tmem106b reduction normalizes some lysosomal phenotypes in Grn +/- mice.

Multi-frequency localization of aberrant brain activity in autism spectrum disorder.

PubMed

Xiang, Jing; Korostenskaja, Milena; Molloy, Cynthia; deGrauw, Xinyao; Leiken, Kimberly; Gilman, Carley; Meinzen-Derr, Jareen; Fujiwara, Hisako; Rose, Douglas F; Mitchell, Terry; Murray, Donna S

2016-01-01

The abnormality of intrinsic brain activity in autism spectrum disorders (ASDs) is still inconclusive. Contradictory results have been found pointing towards hyper-activity or hypo-activity in various brain regions. The present research aims to investigate the spatial and spectral signatures of aberrant brain activity in an unprecedented frequency range of 1-2884 Hz at source levels in ASD using newly developed methods. Seven ASD subjects and age- and gender-matched controls were studied using a high-sampling rate magnetoencephalography (MEG) system. Brain activity in delta (1-4 Hz), theta (4-8 Hz), alpha (8-12 Hz), beta (12-30 Hz), low gamma (30-55 Hz), high gamma (65-90 Hz), ripples (90-200 Hz), high-frequency oscillations (HFOs, 200-1000 Hz), and very high-frequency oscillations (VHFOs, 1000-2884 Hz) was volumetrically localized and measured using wavelet and beamforming. In comparison to controls, ASD subjects had significantly higher odds of alpha activity (8-12 Hz) in the sensorimotor cortex (mu rhythm), and generally high-frequency activity (90-2884 Hz) in the frontal cortex. The source power of HFOs (200-1000 Hz) in the frontal cortex in ASD was significantly elevated as compared with controls. The results suggest that ASD has significantly altered intrinsic brain activity in both low- and high-frequency ranges. Increased intrinsic high-frequency activity in the frontal cortex may play a key role in ASD. Copyright © 2015 The Japanese Society of Child Neurology. Published by Elsevier B.V. All rights reserved.

Morphological and Glucose Metabolism Abnormalities in Alcoholic Korsakoff's Syndrome: Group Comparisons and Individual Analyses

PubMed Central

Pitel, Anne-Lise; Aupée, Anne-Marie; Chételat, Gaël; Mézenge, Florence; Beaunieux, Hélène; de la Sayette, Vincent; Viader, Fausto; Baron, Jean-Claude; Eustache, Francis; Desgranges, Béatrice

2009-01-01

Background Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS). Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. Methodology/Principal Findings Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and 18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. Conclusions/Significance These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker. PMID:19936229

A review of MRI findings in schizophrenia

PubMed Central

Shenton, Martha E.; Dickey, Chandlee C.; Frumin, Melissa; McCarley, Robert W.

2009-01-01

After more than 100 years of research, the neuropathology of schizophrenia remains unknown and this is despite the fact that both Kraepelin (1919/1971: Kraepelin,E., 1919/1971. Dementia praecox. Churchill Livingston Inc., New York) and Bleuler (1911/1950: Bleuler, E., 1911/1950. Dementia praecox or the group of schizophrenias. International Universities Press, New York), who first described ‘dementia praecox’ and the ‘ schizophrenias’, were convinced that schizophrenia would ultimately be linked to an organic brain disorder. Alzheimer (1897: Alzheimer, A., 1897. Beitrage zur pathologischen anatomie der hirnrinde und zur anatomischen grundlage einiger psychosen. Monatsschrift fur Psychiarie und Neurologie. 2, 82–120) was the first to investigate the neuropathology of schizophrenia, though he went on to study more tractable brain diseases. The results of subsequent neuropathological studies were disappointing because of conflicting findings. Research interest thus waned and did not flourish again until 1976, following the pivotal computer assisted tomography (CT) finding of lateral ventricular enlargement in schizophrenia by Johnstone and colleagues. Since that time significant progress has been made in brain imaging, particularly with the advent of magnetic resonance imaging (MRI), beginning with the first MRI study of schizophrenia by Smith and coworkers in 1984 (Smith, R.C., Calderon, M., Ravichandran, G.K., et al. (1984). Nuclear magnetic resonance in schizophrenia: A preliminary study. Psychiatry Res. 12, 137–147). MR in vivo imaging of the brain now confirms brain abnormalities in schizophrenia. The 193 peer reviewed MRI studies reported in the current review span the period from 1988 to August, 2000. This 12 year period has witnessed a burgeoning of MRI studies and has led to more definitive findings of brain abnormalities in schizophrenia than any other time period in the history of schizophrenia research. Such progress in defining the neuropathology of schizophrenia is largely due to advances in in vivo MRI techniques. These advances have now led to the identification of a number of brain abnormalities in schizophrenia. Some of these abnormalities confirm earlier post-mortem findings, and most are small and subtle, rather than large, thus necessitating more advanced and accurate measurement tools. These findings include ventricular enlargement (80% of studies reviewed) and third ventricle enlargement (73% of studies reviewed). There is also preferential involvement of medial temporal lobe structures (74% of studies reviewed), which include the amygdala, hippocampus, and parahippocampal gyrus, and neocortical temporal lobe regions (superior temporal gyrus) (100% of studies reviewed). When gray and white matter of superior temporal gyrus was combined, 67% of studies reported abnormalities. There was also moderate evidence for frontal lobe abnormalities (59% of studies reviewed), particularly prefrontal gray matter and orbitofrontal regions. Similarly, there was moderate evidence for parietal lobe abnormalities (60% of studies reviewed), particularly of the inferior parietal lobule which includes both supramarginal and angular gyri. Additionally, there was strong to moderate evidence for subcortical abnormalities (i.e. cavum septi pellucidi—92% of studies reviewed, basal ganglia—68% of studies reviewed, corpus callosum—63% of studies reviewed, and thalamus—42% of studies reviewed), but more equivocal evidence for cerebellar abnormalities (31% of studies reviewed). The timing of such abnormalities has not yet been determined, although many are evident when a patient first becomes symptomatic. There is, however, also evidence that a subset of brain abnormalities may change over the course of the illness. The most parsimonious explanation is that some brain abnormalities are neurodevelopmental in origin but unfold later in development, thus setting the stage for the development of the symptoms of schizophrenia. Or there may be additional factors, such as stress or neurotoxicity, that occur during adolescence or early adulthood and are necessary for the development of schizophrenia, and may be associated with neurodegenerative changes. Importantly, as several different brain regions are involved in the neuropathology of schizophrenia, new models need to be developed and tested that explain neural circuitry abnormalities effecting brain regions not necessarily structurally proximal to each other but nonetheless functionally interrelated. Future studies will likely benefit from: (1) studying more homogeneous patient groups so that the relationship between MRI findings and clinical symptoms become more meaningful; (2) studying at risk populations such as family members of patients diagnosed with schizophrenia and subjects diagnosed with schizotypal personality disorder in order to define which abnormalities are specific to schizophrenia spectrum disorders, which are the result of epiphenomena such as medication effects and chronic institutionalization, and which are needed for the development of frank psychosis; (3) examining shape differences not detectable from measuring volume alone; (4) applying newer methods such as diffusion tensor imaging to investigate abnormalities in brain connectivity and white matter fiber tracts; and, (5) using methods that analyze brain function (fMRI) and structure simultaneously. PMID:11343862

Connectomics and graph theory analyses: Novel insights into network abnormalities in epilepsy.

PubMed

Gleichgerrcht, Ezequiel; Kocher, Madison; Bonilha, Leonardo

2015-11-01

The assessment of neural networks in epilepsy has become increasingly relevant in the context of translational research, given that localized forms of epilepsy are more likely to be related to abnormal function within specific brain networks, as opposed to isolated focal brain pathology. It is notable that variability in clinical outcomes from epilepsy treatment may be a reflection of individual patterns of network abnormalities. As such, network endophenotypes may be important biomarkers for the diagnosis and treatment of epilepsy. Despite its exceptional potential, measuring abnormal networks in translational research has been thus far constrained by methodologic limitations. Fortunately, recent advancements in neuroscience, particularly in the field of connectomics, permit a detailed assessment of network organization, dynamics, and function at an individual level. Data from the personal connectome can be assessed using principled forms of network analyses based on graph theory, which may disclose patterns of organization that are prone to abnormal dynamics and epileptogenesis. Although the field of connectomics is relatively new, there is already a rapidly growing body of evidence to suggest that it can elucidate several important and fundamental aspects of abnormal networks to epilepsy. In this article, we provide a review of the emerging evidence from connectomics research regarding neural network architecture, dynamics, and function related to epilepsy. We discuss how connectomics may bring together pathophysiologic hypotheses from conceptual and basic models of epilepsy and in vivo biomarkers for clinical translational research. By providing neural network information unique to each individual, the field of connectomics may help to elucidate variability in clinical outcomes and open opportunities for personalized medicine approaches to epilepsy. Connectomics involves complex and rich data from each subject, thus collaborative efforts to enable the systematic and rigorous evaluation of this form of "big data" are paramount to leverage the full potential of this new approach. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Voxel-based morphometry of auditory and speech-related cortex in stutterers.

PubMed

Beal, Deryk S; Gracco, Vincent L; Lafaille, Sophie J; De Nil, Luc F

2007-08-06

Stutterers demonstrate unique functional neural activation patterns during speech production, including reduced auditory activation, relative to nonstutterers. The extent to which these functional differences are accompanied by abnormal morphology of the brain in stutterers is unclear. This study examined the neuroanatomical differences in speech-related cortex between stutterers and nonstutterers using voxel-based morphometry. Results revealed significant differences in localized grey matter and white matter densities of left and right hemisphere regions involved in auditory processing and speech production.

Abnormalities of Object Visual Processing in Body Dysmorphic Disorder

PubMed Central

Feusner, Jamie D.; Hembacher, Emily; Moller, Hayley; Moody, Teena D.

2013-01-01

Background Individuals with body dysmorphic disorder may have perceptual distortions for their appearance. Previous studies suggest imbalances in detailed relative to configural/holistic visual processing when viewing faces. No study has investigated the neural correlates of processing non-symptom-related stimuli. The objective of this study was to determine whether individuals with body dysmorphic disorder have abnormal patterns of brain activation when viewing non-face/non-body object stimuli. Methods Fourteen medication-free participants with DSM-IV body dysmorphic disorder and 14 healthy controls participated. We performed functional magnetic resonance imaging while participants matched photographs of houses that were unaltered, contained only high spatial frequency (high detail) information, or only low spatial frequency (low detail) information. The primary outcome was group differences in blood oxygen level-dependent signal changes. Results The body dysmorphic disorder group showed lesser activity in the parahippocampal gyrus, lingual gyrus, and precuneus for low spatial frequency images. There were greater activations in medial prefrontal regions for high spatial frequency images, although no significant differences when compared to a low-level baseline. Greater symptom severity was associated with lesser activity in dorsal occipital cortex and ventrolateral prefrontal cortex for normal and high spatial frequency images. Conclusions Individuals with body dysmorphic disorder have abnormal brain activation patterns when viewing objects. Hypoactivity in visual association areas for configural and holistic (low detail) elements and abnormal allocation of prefrontal systems for details is consistent with a model of imbalances in global vs. local processing. This may occur not only for appearance but also for general stimuli unrelated to their symptoms. PMID:21557897

Decorticate posture

MedlinePlus

Abnormal posturing - decorticate posture; Traumatic brain injury - decorticate posture ... Brain problem due to drugs, poisoning, or infection Traumatic brain injury Brain problem due to liver failure Increased pressure ...

Abnormal brain chemistry in chronic back pain: an in vivo proton magnetic resonance spectroscopy study.

PubMed

Grachev, I D; Fredrickson, B E; Apkarian, A V

2000-12-15

The neurobiology of chronic pain, including chronic back pain, is unknown. Structural imaging studies of the spine cannot explain all cases of chronic back pain. Functional brain imaging studies indicate that the brain activation patterns are different between chronic pain patients and normal subjects, and the thalamus, and prefrontal and cingulate cortices are involved in some types of chronic pain. Animal models of chronic pain suggest abnormal spinal cord chemistry. Does chronic pain cause brain chemistry changes? We examined brain chemistry changes in patients with chronic back pain using in vivo single- voxel proton magnetic resonance spectroscopy ((1)H-MRS). In vivo (1)H-MRS was used to measure relative concentrations of N-acetyl aspartate, creatine, choline, glutamate, glutamine, gamma-aminobutyric acid, inositol, glucose and lactate in relation to the concentration of creatine. These measurements were performed in six brain regions of nine chronic low back pain patients and 11 normal volunteers. All chronic back pain subjects underwent clinical evaluation and perceptual measures of pain and anxiety. We show that chronic back pain alters the human brain chemistry. Reductions of N-acetyl aspartate and glucose were demonstrated in the dorsolateral prefrontal cortex. Cingulate, sensorimotor, and other brain regions showed no chemical concentration differences. In chronic back pain, the interrelationship between chemicals within and across brain regions was abnormal, and there was a specific relationship between regional chemicals and perceptual measures of pain and anxiety. These findings provide direct evidence of abnormal brain chemistry in chronic back pain, which may be useful in diagnosis and future development of more effective pharmacological treatments.

Influence of History of Brain Disease or Brain Trauma on Psychopathological Abnormality in Young Male in Korea : Analysis of Multiphasic Personal Inventory Test

PubMed Central

Paik, Ho Kyu; Oh, Chang-Hyun; Choi, Kang; Kim, Chul-Eung; Yoon, Seung Hwan

2011-01-01

Objective The purpose of this study is to confirm whether brain disease or brain trauma actually affect psychopathology in young male group in Korea. Methods The authors manually reviewed the result of Korean military multiphasic personal inventory (KMPI) in the examination of conscription in Korea from January 2008 to May 2010. There were total 237 young males in this review. Normal volunteers group (n=150) was composed of those who do not have history of brain disease or brain trauma. Brain disease group (n=33) was consisted of those with history of brain disease. Brain trauma group (n=54) was consisted of those with history of brain trauma. The results of KMPI in each group were compared. Results Abnormal results of KMPI were found in both brain disease and trauma groups. In the brain disease group, higher tendencies of faking bad response, anxiety, depression, somatization, personality disorder, schizophrenic and paranoid psychopathy was observed and compared to the normal volunteers group. In the brain trauma group, higher tendencies of faking-good, depression, somatization and personality disorder was observed and compared to the normal volunteers group. Conclusion Young male with history of brain disease or brain trauma may have higher tendencies to have abnormal results of multiphasic personal inventory test compared to young male without history of brain disease or brain trauma, suggesting that damaged brain may cause psychopathology in young male group in Korea. PMID:22053230

Localization of deformations within the amygdala in individuals with psychopathy.

PubMed

Yang, Yaling; Raine, Adrian; Narr, Katherine L; Colletti, Patrick; Toga, Arthur W

2009-09-01

Despite the repeated findings of impaired fear conditioning and affective recognition in psychopathic individuals, there has been a paucity of brain imaging research on the amygdala and no evidence suggesting which regions within the amygdala may be structurally compromised in individuals with psychopathy. To detect global and regional anatomical abnormalities in the amygdala in individuals with psychopathy. Cross-sectional design using structural magnetic resonance imaging. Participants were recruited from high-risk communities (temporary employment agencies) in the Los Angeles, California, area and underwent imaging at a hospital research facility at the University of Southern California. Twenty-seven psychopathic individuals as defined by the Hare Psychopathy Checklist-Revised and 32 normal controls matched on age, sex, and ethnicity. Amygdala volumes were examined using traditional volumetric analyses and surface-based mesh modeling methods were used to localize regional surface deformations. Individuals with psychopathy showed significant bilateral volume reductions in the amygdala compared with controls (left, 17.1%; right, 18.9%). Surface deformations were localized in regions in the approximate vicinity of the basolateral, lateral, cortical, and central nuclei of the amygdala. Significant correlations were found between reduced amygdala volumes and increased total and facet psychopathy scores, with correlations strongest for the affective and interpersonal facets of psychopathy. Results provide the first evidence, to our knowledge, of focal amygdala abnormalities in psychopathic individuals and corroborate findings from previous lesion studies. Findings support prior hypotheses of amygdala deficits in individuals with psychopathy and indicate that amygdala abnormalities contribute to emotional and behavioral symptoms of psychopathy.

DTI-measured white matter abnormalities in adolescents with Conduct Disorder

PubMed Central

Haney-Caron, Emily; Caprihan, Arvind; Stevens, Michael C.

2013-01-01

Emerging research suggests that antisocial behavior in youth is linked to abnormal brain white matter microstructure, but the extent of such anatomical connectivity abnormalities remain largely untested because previous Conduct Disorder (CD) studies typically have selectively focused on specific frontotemporal tracts. This study aimed to replicate and extend previous frontotemporal diffusion tensor imaging (DTI) findings to determine whether noncomorbid CD adolescents have white matter microstructural abnormalities in major white matter tracts across the whole brain. Seventeen CD-diagnosed adolescents recruited from the community were compared to a group of 24 non-CD youth which did not differ in average age (12–18) or gender proportion. Tract-based spatial statistics (TBSS) fractional anisotropy (FA), axial diffusivity (AD), and radial diffusivity (RD) measurements were compared between groups using FSL nonparametric two-sample t test, clusterwise whole-brain corrected, p<.05. CD FA and AD deficits were widespread, but unrelated to gender, verbal ability, or CD age of onset. CD adolescents had significantly lower FA and AD values in frontal lobe and temporal lobe regions, including frontal lobe anterior/superior corona radiata, and inferior longitudinal and fronto-occpital fasciculi passing through the temporal lobe. The magnitude of several CD FA deficits was associated with number of CD symptoms. Because AD, but not RD, differed between study groups, abnormalities of axonal microstructure in CD rather than myelination are suggested. This study provides evidence that adolescent antisocial disorder is linked to abnormal white matter microstructure in more than just the uncinate fasciulcus as identified in previous DTI studies, or frontotemporal brain structures as suggested by functional neuroimaging studies. Instead, neurobiological risk specific to antisociality in adolescence is linked to microstructural abnormality in numerous long-range white matter connections among many diverse different brain regions. PMID:24139595

Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports.

PubMed

Fain, Emily T; Mannion, Melissa; Pope, Elena; Young, Daniel W; Laxer, Ronald M; Cron, Randy Q

2011-07-29

Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition.

Brain cavernomas associated with en coup de sabre linear scleroderma: Two case reports

PubMed Central

2011-01-01

Linear scleroderma is a form of localized scleroderma that primarily affects the pediatric population. When it occurs on the scalp or forehead, it is termed "en coup de sabre". In the en coup de sabre subtype, many extracutaneous associations, mostly neurological, have been described. A patient with linear scleroderma en coup de sabre was noted to have ipsilateral brain cavernomas by magnetic resonance imaging. Using a worldwide pediatric rheumatology electronic list-serve, another patient with the same 2 conditions was identified. These two patients are reported in this study. Consideration of neuroimaging studies to disclose abnormal findings in patients with linear scleroderma en coup de sabre is important for potentially preventing and treating neurological manifestations associated with this condition. PMID:21801349

Understanding Brain Tumors

MedlinePlus

... to Know About Brain Tumors . What is a Brain Tumor? A brain tumor is an abnormal growth
 ... Tumors” from Frankly Speaking Frankly Speaking About Cancer: Brain Tumors Download the full book Questions to ask ...

Genetic abnormality predicts benefit for a rare brain tumor

Cancer.gov

A clinical trial has shown that addition of chemotherapy to radiation therapy leads to a near doubling of median survival time in patients with a form of brain tumor (oligodendroglioma) that carries a chromosomal abnormality called the 1p19q co-deletion.

Solitary tuberculous brain lesions: 24 new cases and a review of the literature.

PubMed

Psimaras, D; Bonnet, C; Heinzmann, A; Cárdenas, G; Hernández José Luis, S; Tungaria, A; Behari, S; Lacrois, D; Mokhtari, K; Karantoni, E; Sokrab Tag, E; Idris Mohamed, N; Sönmez, G; Caumes, E; Roze, E

2014-01-01

A solitary tuberculous brain lesion (STBL) can be difficult to distinguish from a glioma, metastasis or other infectious disease, especially from a pyogenic brain abscess. We analyzed the clinical characteristics, diagnostic procedures and outcomes of 24 patients with STBL diagnosed in three centers from France, India and Mexico. We also reviewed 92 STBL cases previously reported in the literature. General symptoms were found in 54% of our patients, including enlarged lymph nodes in 20%. Cerebrospinal fluid was typically abnormal, with lymphocytic pleocytosis and a high protein level. The lung CT scan was abnormal in 56% of patients, showing lymphadenopathy or pachipleuritis. Brain MRI or CT was always abnormal, showing contrast-enhanced lesions. Typically, MRI abnormalities were hypointense on T1-weighted sequences, while T2-weighted sequences showed both a peripheral hypersignal and a central hyposignal. The diagnosis was documented microbiologically or supported histologically in 71% of cases. Clinical outcome was good in 83% of cases. Copyright © 2014 Elsevier Masson SAS. All rights reserved.

Neuroimaging studies in schizophrenia: an overview of research from Asia.

PubMed

Narayanaswamy, Janardhanan C; Venkatasubramanian, Ganesan; Gangadhar, Bangalore N

2012-10-01

Neuroimaging studies in schizophrenia help clarify the neural substrates underlying the pathogenesis of this neuropsychiatric disorder. Contemporary brain imaging in schizophrenia is predominated by magnetic resonance imaging (MRI)-based research approaches. This review focuses on the various imaging studies from India and their relevance to the understanding of brain abnormalities in schizophrenia. The existing studies are predominantly comprised of structural MRI reports involving region-of-interest and voxel-based morphometry approaches, magnetic resonance spectroscopy and single-photon emission computed tomography/positron emission tomography (SPECT/PET) studies. Most of these studies are significant in that they have evaluated antipsychotic-naïve schizophrenia patients--a relatively difficult population to obtain in contemporary research. Findings of these studies offer robust support to the existence of significant brain abnormalities at very early stages of the disorder. In addition, theoretically relevant relationships between these brain abnormalities and developmental aberrations suggest possible neurodevelopmental basis for these brain deficits.

Brain anomalies in velo-cardio-facial syndrome

DOE Office of Scientific and Technical Information (OSTI.GOV)

Mitnick, R.J.; Bello, J.A.; Shprintzen, R.J.

Magnetic resonance imaging of the brain in 11 consecutively referred patients with velo-cardio-facial syndrome (VCF) showed anomalies in nine cases including small vermis, cysts adjacent to the frontal horns, and small posterior fossa. Focal signal hyperintensities in the white matter on long TR images were also noted. The nine patients showed a variety of behavioral abnormalities including mild development delay, learning disabilities, and characteristic personality traits typical of this common multiple anomaly syndrome which has been related to a microdeletion at 22q11. Analysis of the behavorial findings showed no specific pattern related to the brain anomalies, and the patients withmore » VCF who did not have detectable brain lesions also had behavioral abnormalities consistent with VCF. The significance of the lesions is not yet known, but the high prevalence of anomalies in this sample suggests that structural brain abnormalities are probably common in VCF. 25 refs.« less

Central nervous system abnormalities in Fanconi anaemia: patterns and frequency on magnetic resonance imaging

PubMed Central

Alston, Robert; Wright, Neville B; Chandler, Kate; Bonney, Denise; Wynn, Robert F; Will, Andrew M; Punekar, Maqsood; Loughran, Sean; Kilday, John-Paul; Schindler, Detlev; Patel, Leena; Meyer, Stefan

2015-01-01

Objective: Fanconi anaemia (FA) is an inherited disease associated with congenital and developmental abnormalities resulting from the disruption of a multigenic DNA damage response pathway. This study aimed to define the MRI appearances of the brain in patients with FA in correlation with their genetic and clinical features. Methods: A review of the brain MRI in 20 patients with FA was performed. Pituitary size and frequencies of the radiological findings of individuals with FA and age-matched controls were determined. Results: Abnormalities were identified in 18 (90%) patients with FA, the commonest being a small pituitary (68%, p < 0.01 females and p < 0.001 males). In five cases (25%, p = 0.02), the pituitary morphology was also abnormal. Posterior fossa abnormalities were seen in six cases (30%, p = 0.01) including Chiari I malformation (n = 3), Dandy–Walker variant (n = 2) and cerebellar atrophy (n = 2). Six patients (30%, p = 0.01) had morphological structural variation of the corpus callosum (CC). Conclusion: The incidence of central nervous system (CNS) abnormalities in FA is higher than previously reported, with a midline predominance that points to impact in the early stages of CNS development. MRI brain imaging is important for endocrine assessment and pre-transplant evaluation and can make an important contribution to clinical decision-making. Advances in knowledge: The incidence of brain structural abnormalities in FA is higher than previously reported, with abnormalities of the posterior fossa, CC and pituitary being common. There is an association with gender and reduction in pituitary size which does not strongly correlate with biochemically evident endocrine abnormality. PMID:26369989

TSPO Expression and Brain Structure in the Psychosis Spectrum.

PubMed

Hafizi, Sina; Guma, Elisa; Koppel, Alex; Da Silva, Tania; Kiang, Michael; Houle, Sylvain; Wilson, Alan A; Rusjan, Pablo M; Chakravarty, M Mallar; Mizrahi, Romina

2018-06-12

Psychosis is associated with abnormal structural changes in the brain including decreased regional brain volumes and abnormal brain morphology. However, the underlying causes of these structural abnormalities are less understood. The immune system, including microglial activation, has been implicated in the pathophysiology of psychosis. Although previous studies have suggested a connection between peripheral proinflammatory cytokines and structural brain abnormalities in schizophrenia, no in-vivo studies have investigated whether microglial activation is also linked to brain structure alterations previously observed in schizophrenia and its putative prodrome. In this study, we investigated the link between mitochondrial 18kDa translocator protein (TSPO) and structural brain characteristics (i.e. regional brain volume, cortical thickness, and hippocampal shape) in key brain regions such as dorsolateral prefrontal cortex and hippocampus of a large group of participants (N = 90) including individuals at clinical high risk (CHR) for psychosis, first-episode psychosis (mostly antipsychotic naïve) patients, and healthy volunteers. The participants underwent structural brain MRI scan and [ 18 F]FEPPA positron emission tomography (PET) targeting TSPO. A significant [ 18 F]FEPPA binding-by-group interaction was observed in morphological measures across the left hippocampus. In first-episode psychosis, we observed associations between [ 18 F]FEPPA V T (total volume of distribution) and outward and inward morphological alterations, respectively, in the dorsal and ventro-medial portions of the left hippocampus. These associations were not significant in CHR or healthy volunteers. There was no association between [ 18 F]FEPPA V T and other structural brain characteristics. Our findings suggest a link between TSPO expression and alterations in hippocampal morphology in first-episode psychosis. Copyright © 2018. Published by Elsevier Inc.

Scleroderma en coup de sabre with recurrent episodes of brain hemorrhage.

PubMed

Takahashi, Takehiro; Asano, Yoshihide; Oka, Tomonori; Miyagaki, Tomomitsu; Tamaki, Zenshiro; Nonaka, Senshu; Sato, Shinichi

2016-02-01

We report a 39-year-old man referred to our facility with linear sclerotic lesions along the several Blaschko's lines of the scalp. A year before the referral, he had had an episode of brain hemorrhage, although there was no evidence of vascular malformation or any other risk factors of brain hemorrhage for his young age. On the diagnosis of scleroderma en coup de sabre, prednisolone intake was initiated, and the skin lesions were well controlled. However, in the course of our follow up, he had another episode of brain hemorrhage, again without any evidence of cerebral vascular abnormalities. Organic intracranial abnormalities in this disease are well-documented, but there have been few reports on comorbid recurrent brain hemorrhages. We herein discuss the possible relationship of the skin lesions with the brain hemorrhages in our case, taking notice of the implication of developmental abnormalities behind these apparently independent phenomena inside and outside the cranium. © 2015 Japanese Dermatological Association.

Is Dyslexia a Brain Disorder?

PubMed Central

Parrila, Rauno

2018-01-01

Specific word reading difficulty, commonly termed ‘developmental dyslexia’, refers to the low end of the word reading skill distribution but is frequently considered to be a neurodevelopmental disorder. This term implies that brain development is thought to be disrupted, resulting in an abnormal and dysfunctional brain. We take issue with this view, pointing out that there is no evidence of any obvious neurological abnormality in the vast majority of cases of word reading difficulty cases. The available relevant evidence from neuroimaging studies consists almost entirely of correlational and group-differences studies. However, differences in brains are certain to exist whenever differences in behavior exist, including differences in ability and performance. Therefore, findings of brain differences do not constitute evidence for abnormality; rather, they simply document the neural substrate of the behavioral differences. We suggest that dyslexia is best viewed as one of many expressions of ordinary ubiquitous individual differences in normal developmental outcomes. Thus, terms such as “dysfunctional” or “abnormal” are not justified when referring to the brains of persons with dyslexia. PMID:29621138

Brain Tumors

MedlinePlus

A brain tumor is a growth of abnormal cells in the tissues of the brain. Brain tumors can be benign, with no cancer cells, ... cancer cells that grow quickly. Some are primary brain tumors, which start in the brain. Others are ...

Brain abnormalities and neurodevelopmental delay in congenital heart disease: systematic review and meta-analysis.

PubMed

Khalil, A; Suff, N; Thilaganathan, B; Hurrell, A; Cooper, D; Carvalho, J S

2014-01-01

Studies have demonstrated an association between congenital heart disease (CHD) and neurodevelopmental delay. Neuroimaging studies have also demonstrated a high incidence of preoperative brain abnormalities. The aim of this study was to perform a systematic review to quantify the non-surgical risk of brain abnormalities and of neurodevelopmental delay in infants with CHD. MEDLINE, EMBASE and The Cochrane Library were searched electronically without language restrictions, utilizing combinations of the terms congenital heart, cardiac, neurologic, neurodevelopment, magnetic resonance imaging, ultrasound, neuroimaging, autopsy, preoperative and outcome. Reference lists of relevant articles and reviews were hand-searched for additional reports. Cohort and case-control studies were included. Studies reporting neurodevelopmental outcomes and/or brain lesions on neuroimaging in infants with CHD before heart surgery were included. Cases of chromosomal or genetic abnormalities, case reports and editorials were excluded. Between-study heterogeneity was assessed using the I(2) test. The search yielded 9129 citations. Full text was retrieved for 119 and the following were included in the review: 13 studies (n = 425 cases) reporting on brain abnormalities either preoperatively or in those who did not undergo congenital cardiac surgery and nine (n = 512 cases) reporting preoperative data on neurodevelopmental assessment. The prevalence of brain lesions on neuroimaging was 34% (95% CI, 24-46; I(2) = 0%) in transposition of the great arteries, 49% (95% CI, 25-72; I(2) = 65%) in left-sided heart lesions and 46% (95% CI, 40-52; I(2) =18.1%) in mixed/unspecified cardiac lesions, while the prevalence of neurodevelopmental delay was 42% (95% CI, 34-51; I(2) = 68.9). In the absence of chromosomal or genetic abnormalities, infants with CHD are at increased risk of brain lesions as revealed by neuroimaging and of neurodevelopmental delay. These findings are independent of the surgical risk, but it is unclear whether the time of onset is fetal or postnatal. Copyright © 2013 ISUOG. Published by John Wiley & Sons Ltd.

Structural brain abnormalities in patients with inflammatory illness acquired following exposure to water-damaged buildings: a volumetric MRI study using NeuroQuant®.

PubMed

Shoemaker, Ritchie C; House, Dennis; Ryan, James C

2014-01-01

Executive cognitive and neurologic abnormalities are commonly seen in patients with a chronic inflammatory response syndrome (CIRS) acquired following exposure to the interior environment of water-damaged buildings (WDB), but a clear delineation of the physiologic or structural basis for these abnormalities has not been defined. Symptoms of affected patients routinely include headache, difficulty with recent memory, concentration, word finding, numbness, tingling, metallic taste and vertigo. Additionally, persistent proteomic abnormalities in inflammatory parameters that can alter permeability of the blood-brain barrier, such as C4a, TGFB1, MMP9 and VEGF, are notably present in cases of CIRS-WDB compared to controls, suggesting a consequent inflammatory injury to the central nervous system. Findings of gliotic areas in MRI scans in over 45% of CIRS-WDB cases compared to 5% of controls, as well as elevated lactate and depressed ratios of glutamate to glutamine, are regularly seen in MR spectroscopy of cases. This study used the volumetric software program NeuroQuant® (NQ) to determine specific brain structure volumes in consecutive patients (N=17) seen in a medical clinic specializing in inflammatory illness. Each of these patients presented for evaluation of an illness thought to be associated with exposure to WDB, and received an MRI that was evaluated by NQ. When compared to those of a medical control group (N=18), statistically significant differences in brain structure proportions were seen for patients in both hemispheres of two of the eleven brain regions analyzed; atrophy of the caudate nucleus and enlargement of the pallidum. In addition, the left amygdala and right forebrain were also enlarged. These volumetric abnormalities, in conjunction with concurrent abnormalities in inflammatory markers, suggest a model for structural brain injury in "mold illness" based on increased permeability of the blood-brain barrier due to chronic, systemic inflammation. Copyright © 2014 Elsevier Inc. All rights reserved.

Brain Growth Rate Abnormalities Visualized in Adolescents with Autism

PubMed Central

Hua, Xue; Thompson, Paul M.; Leow, Alex D.; Madsen, Sarah K.; Caplan, Rochelle; Alger, Jeffry R.; O’Neill, Joseph; Joshi, Kishori; Smalley, Susan L.; Toga, Arthur W.; Levitt, Jennifer G.

2014-01-01

Autism spectrum disorder (ASD) is a heterogeneous disorder of brain development with wide-ranging cognitive deficits. Typically diagnosed before age 3, ASD is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared to those of typically developing children and adolescents. Using tensor-based morphometry (TBM), we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and 7 typically developing boys (mean age/inter-scan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole-brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (p = 0.03, corrected), especially in the parietal (p = 0.008), temporal (p = 0.03) and occipital lobes (p =0.02). We also visualized abnormal overgrowth in autism in some gray matter structures, such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. TBM revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. PMID:22021093

Brain growth rate abnormalities visualized in adolescents with autism.

PubMed

Hua, Xue; Thompson, Paul M; Leow, Alex D; Madsen, Sarah K; Caplan, Rochelle; Alger, Jeffry R; O'Neill, Joseph; Joshi, Kishori; Smalley, Susan L; Toga, Arthur W; Levitt, Jennifer G

2013-02-01

Autism spectrum disorder is a heterogeneous disorder of brain development with wide ranging cognitive deficits. Typically diagnosed before age 3, autism spectrum disorder is behaviorally defined but patients are thought to have protracted alterations in brain maturation. With longitudinal magnetic resonance imaging (MRI), we mapped an anomalous developmental trajectory of the brains of autistic compared with those of typically developing children and adolescents. Using tensor-based morphometry, we created 3D maps visualizing regional tissue growth rates based on longitudinal brain MRI scans of 13 autistic and seven typically developing boys (mean age/interscan interval: autism 12.0 ± 2.3 years/2.9 ± 0.9 years; control 12.3 ± 2.4/2.8 ± 0.8). The typically developing boys demonstrated strong whole brain white matter growth during this period, but the autistic boys showed abnormally slowed white matter development (P = 0.03, corrected), especially in the parietal (P = 0.008), temporal (P = 0.03), and occipital lobes (P = 0.02). We also visualized abnormal overgrowth in autism in gray matter structures such as the putamen and anterior cingulate cortex. Our findings reveal aberrant growth rates in brain regions implicated in social impairment, communication deficits and repetitive behaviors in autism, suggesting that growth rate abnormalities persist into adolescence. Tensor-based morphometry revealed persisting growth rate anomalies long after diagnosis, which has implications for evaluation of therapeutic effects. Copyright © 2011 Wiley Periodicals, Inc.

Magnetic resonance imaging findings in pediatric bilateral vocal fold dysfunction.

PubMed

Steiner, Joel I; Fink, A Michelle; Berkowitz, Robert G

2013-07-01

We studied the findings of brain magnetic resonance imaging (MRI) in infants with idiopathic congenital bilateral vocal fold dysfunction (CBVFD). We performed a retrospective investigation of a case series. We identified 26 children (14 male, 12 female) over 11 years. Three children were excluded. Thirteen patients required airway interventions, including continuous positive airway pressure (4 patients), endotracheal intubation (1), and tracheostomy (8). The findings on brain MRI were abnormal in 8 patients (35%). Tracheostomy was required in 3 patients (38%) with abnormal MRI findings, as compared with 5 of 15 patients (33%) with normal MRI findings. The MRI abnormalities involved evidence of white matter injury (2), abnormal white matter signal (1), subdural blood (3), cerebral swelling (1), and perisylvian polymicrogyria (1). The cranial ultrasound findings were abnormal in 4 of 11 patients. The MRI findings were abnormal in 2 of 7 children in whom the cranial ultrasound findings were normal, and in 2 of the 4 patients in whom the cranial ultrasound findings were abnormal. The MRI abnormalities were nonspecific; however, they may indicate unrecognized perinatal intracranial injury as being related to CBVFD. In addition, MRI may reveal an underlying structural brain anomaly. Cranial ultrasound has poor sensitivity and specificity. Hence, MRI should be considered as part of the routine assessment of neonates with CBVFD.

P300 event-related potentials in children with dyslexia.

PubMed

Papagiannopoulou, Eleni A; Lagopoulos, Jim

2017-04-01

To elucidate the timing and the nature of neural disturbances in dyslexia and to further understand the topographical distribution of these, we examined entire brain regions employing the non-invasive auditory oddball P300 paradigm in children with dyslexia and neurotypical controls. Our findings revealed abnormalities for the dyslexia group in (i) P300 latency, globally, but greatest in frontal brain regions and (ii) decreased P300 amplitude confined to the central brain regions (Fig. 1). These findings reflect abnormalities associated with a diminished capacity to process mental workload as well as delayed processing of this information in children with dyslexia. Furthermore, the topographical distribution of these findings suggests a distinct spatial distribution for the observed P300 abnormalities. This information may be useful in future therapeutic or brain stimulation intervention trials.

Technetium-99m-HMPAO SPECT, CT and MRI in the evaluation of patients with chronic traumatic brain injury: a correlation with neuropsychological performance.

PubMed

Ichise, M; Chung, D G; Wang, P; Wortzman, G; Gray, B G; Franks, W

1994-02-01

The purposes of this study were: (1) to compare 99mTc-hexamethylpropyleneamineoxime (HMPAO) SPECT with CT and MRI in chronic traumatic brain injury (TBI) patients and (2) to correlate both functional and structural neuroimaging measurements of brain damage with neuropsychological (NP) performance. Twenty-nine patients (minor TBI, n = 15 and major TBI, n = 14) and 17 normal controls (NC) underwent HMPAO SPECT, CT, MRI and NP testing. Imaging data were analyzed both visually and quantitatively. Nineteen (66%) patients showed 42 abnormalities on SPECT images, whereas 13 (45%) and 10 (34%) patients showed 29 abnormalities on MRI and 24 abnormalities on CT. SPECT detected relatively more abnormalities than CT or MRI in the minor TBI subgroup. The TBI group showed impairment on 11 tests for memory, attention and executive function. Of these, the anterior-posterior ratio (APR) correlated with six tests, whereas the ventricle-to-brain ratio (VBR), a known structural index of a poor NP outcome, correlated with only two tests. In evaluating chronic TBI patients, HMPAO SPECT, as a complement to CT or MRI, may play a useful role by demonstrating brain dysfunction in morphologically intact brain regions and providing objective evidence for some of the impaired NP performance.

Abnormal Spontaneous Brain Activity in Patients With Anisometropic Amblyopia Using Resting-State Functional Magnetic Resonance Imaging.

PubMed

Tang, Angcang; Chen, Taolin; Zhang, Junran; Gong, Qiyong; Liu, Longqian

2017-09-01

To explore the abnormality of spontaneous activity in patients with anisometropic amblyopia under resting-state functional magnetic resonance imaging (Rs-fMRI). Twenty-four participants were split into two groups. The anisometropic amblyopia group had 10 patients, all of whom had anisometropic amblyopia of the right eye, and the control group had 14 healthy subjects. All participants underwent Rs-fMRI scanning. Measurement of amplitude of low frequency fluctuations of the brain, which is a measure of the amplitudes of spontaneous brain activity, was used to investigate brain changes between the anisometropic amblyopia and control groups. Compared with an age- and gender-matched control group, the anisometropic amblyopia group showed increased amplitude of low frequency fluctuations of spontaneous brain activity in the left superior temporal gyrus, the left inferior parietal lobe, the left pons, and the right inferior semi-lunar lobe. The anisometropic amblyopia group also showed decreased amplitude of low frequency fluctuations in the bilateral medial frontal gyrus. This study demonstrated abnormal spontaneous brain activities in patients with anisometropic amblyopia under Rs-fMRI, and these abnormalities might contribute to the neuropathological mechanisms of anisometropic amblyopia. [J Pediatr Ophthalmol Strabismus. 2017;54(5):303-310.]. Copyright 2017, SLACK Incorporated.

Identification of elevated urea as a severe, ubiquitous metabolic defect in the brain of patients with Huntington's disease.

PubMed

Patassini, Stefano; Begley, Paul; Reid, Suzanne J; Xu, Jingshu; Church, Stephanie J; Curtis, Maurice; Dragunow, Mike; Waldvogel, Henry J; Unwin, Richard D; Snell, Russell G; Faull, Richard L M; Cooper, Garth J S

Huntington's disease (HD) is a neurodegenerative disorder wherein the aetiological defect is a mutation in the Huntington's gene (HTT), which alters the structure of the huntingtin protein through the lengthening of a polyglutamine tract and initiates a cascade that ultimately leads to dementia and premature death. However, neurodegeneration typically manifests in HD only in middle age, and processes linking the causative mutation to brain disease are poorly understood. Here, our objective was to elucidate further the processes that cause neurodegeneration in HD, by measuring levels of metabolites in brain regions known to undergo varying degrees of damage. We applied gas-chromatography/mass spectrometry-based metabolomics in a case-control study of eleven brain regions in short post-mortem-delay human tissue from nine well-characterized HD patients and nine controls. Unexpectedly, a single major abnormality was evident in all eleven brain regions studied across the forebrain, midbrain and hindbrain, namely marked elevation of urea, a metabolite formed in the urea cycle by arginase-mediated cleavage of arginine. Urea cycle activity localizes primarily in the liver, where it functions to incorporate protein-derived amine-nitrogen into urea for recycling or urinary excretion. It also occurs in other cell-types, but systemic over-production of urea is not known in HD. These findings are consistent with impaired local urea regulation in brain, by up-regulation of synthesis and/or defective clearance. We hypothesize that defective brain urea metabolism could play a substantive role in the pathogenesis of neurodegeneration, perhaps via defects in osmoregulation or nitrogen metabolism. Brain urea metabolism is therefore a target for generating novel monitoring/imaging strategies and/or therapeutic interventions aimed at ameliorating the impact of HD in patients. Copyright © 2015 Elsevier Inc. All rights reserved.

Enuresis as a Premorbid Developmental Marker of Schizophrenia

ERIC Educational Resources Information Center

Hyde, Thomas M.; Deep-Soboslay, Amy; Iglesias, Bianca; Callicott, Joseph H.; Gold, James M.; Meyer-Lindenberg, Andreas; Honea, Robyn A.; Bigelow, Llewellyn B.; Egan, Michael F.; Emsellem, Esther M.; Weinberger, Daniel R.

2008-01-01

There is comparatively little information about premorbid maturational brain abnormalities in schizophrenia (SCZ). We investigated whether a history of childhood enuresis, a well-established marker of neurodevelopmental delay, is associated with SCZ and with measures of brain abnormalities also associated with SCZ. A Diagnostic and Statistical…

Morphometric Brain Abnormalities in Boys with Conduct Disorder

ERIC Educational Resources Information Center

Huebner, Thomas; Vloet, Timo D.; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R.; Herpertz, Sabine C.; Herpertz-Dahlmann, Beate

2008-01-01

Conduct disorder (CD) is associated with antisocial personality behavior that violates the basic rights of others. Results, on examining the structural brain aberrations in boys' CD, show that boys with CD and cormobid attention-deficit/hyperactivity disorder showed abnormalities in frontolimbic areas that could contribute to antisocial…

Cortical thickness as a contributor to abnormal oscillations in schizophrenia?☆

PubMed Central

Edgar, J. Christopher; Chen, Yu-Han; Lanza, Matthew; Howell, Breannan; Chow, Vivian Y.; Heiken, Kory; Liu, Song; Wootton, Cassandra; Hunter, Michael A.; Huang, Mingxiong; Miller, Gregory A.; Cañive, José M.

2013-01-01

Introduction Although brain rhythms depend on brain structure (e.g., gray and white matter), to our knowledge associations between brain oscillations and structure have not been investigated in healthy controls (HC) or in individuals with schizophrenia (SZ). Observing function–structure relationships, for example establishing an association between brain oscillations (defined in terms of amplitude or phase) and cortical gray matter, might inform models on the origins of psychosis. Given evidence of functional and structural abnormalities in primary/secondary auditory regions in SZ, the present study examined how superior temporal gyrus (STG) structure relates to auditory STG low-frequency and 40 Hz steady-state activity. Given changes in brain activity as a function of age, age-related associations in STG oscillatory activity were also examined. Methods Thirty-nine individuals with SZ and 29 HC were recruited. 40 Hz amplitude-modulated tones of 1 s duration were presented. MEG and T1-weighted sMRI data were obtained. Using the sources localizing 40 Hz evoked steady-state activity (300 to 950 ms), left and right STG total power and inter-trial coherence were computed. Time–frequency group differences and associations with STG structure and age were also examined. Results Decreased total power and inter-trial coherence in SZ were observed in the left STG for initial post-stimulus low-frequency activity (~ 50 to 200 ms, ~ 4 to 16 Hz) as well as 40 Hz steady-state activity (~ 400 to 1000 ms). Left STG 40 Hz total power and inter-trial coherence were positively associated with left STG cortical thickness in HC, not in SZ. Left STG post-stimulus low-frequency and 40 Hz total power were positively associated with age, again only in controls. Discussion Left STG low-frequency and steady-state gamma abnormalities distinguish SZ and HC. Disease-associated damage to STG gray matter in schizophrenia may disrupt the age-related left STG gamma-band function–structure relationships observed in controls. PMID:24371794

Neonatal Brain Pathology Predicts Adverse Attention and Processing Speed Outcomes in Very Preterm and/or Very Low Birth Weight Children

PubMed Central

Murray, Andrea L; Scratch, Shannon E; Thompson, Deanne K; Inder, Terrie E; Doyle, Lex W; Anderson, Jacqueline F. I.; Anderson, Peter J

2014-01-01

Objective This study aimed to examine attention and processing speed outcomes in very preterm (VPT; <32 weeks' gestational age) or very low birth weight (VLBW; <1500 g) children, and to assess the ability of brain abnormalities measured by neonatal magnetic resonance imaging (MRI) to predict outcome in these domains. Methods A cohort of 198 children born <30 weeks' gestational age and/or <1250 g and 70 term controls were examined. Neonatal MRI scans at term equivalent age were quantitatively assessed for white matter, cortical gray matter, deep gray matter, and cerebellar abnormalities. Attention and processing speed were assessed at 7 years using standardized neuropsychological tests. Group differences were tested in attention and processing speed, and the relationships between these cognitive domains and brain abnormalities at birth were investigated. Results At 7 years of age, the VPT/VLBW group performed significantly poorer than term controls on all attention and processing speed outcomes. Associations between adverse attention and processing speed performances at 7 years and higher neonatal brain abnormality scores were found; in particular, white matter and deep gray matter abnormalities were reasonable predictors of long-term cognitive outcomes. Conclusion Attention and processing speed are significant areas of concern in VPT/VLBW children. This is the first study to show that adverse attention and processing speed outcomes at 7 years are associated with neonatal brain pathology. PMID:24708047

Neonatal brain pathology predicts adverse attention and processing speed outcomes in very preterm and/or very low birth weight children.

PubMed

Murray, Andrea L; Scratch, Shannon E; Thompson, Deanne K; Inder, Terrie E; Doyle, Lex W; Anderson, Jacqueline F I; Anderson, Peter J

2014-07-01

This study aimed to examine attention and processing speed outcomes in very preterm (VPT; < 32 weeks' gestational age) or very low birth weight (VLBW; < 1,500 g) children, and to determine whether brain abnormality measured by neonatal MRI can be used to predict outcome in these domains. A cohort of 198 children born < 30 weeks' gestational age and/or < 1,250 g and 70 term controls were examined. Neonatal MRI scans at term equivalent age were quantitatively assessed for white matter, cortical gray matter, deep gray matter, and cerebellar abnormalities. Attention and processing speed were assessed at 7 years using standardized neuropsychological tests. Group differences were tested in attention and processing speed, and the relationships between these cognitive domains and brain abnormalities at birth were investigated. At 7 years of age, the VPT/VLBW group performed significantly poorer than term controls on all attention and processing speed outcomes. Associations between adverse attention and processing speed performances at 7 years and higher neonatal brain abnormality scores were found; in particular, white matter and deep gray matter abnormalities were reasonable predictors of long-term cognitive outcomes. Attention and processing speed are significant areas of concern in VPT/VLBW children. This is the first study to show that adverse attention and processing speed outcomes at 7 years are associated with neonatal brain pathology.

Neuroimaging evidence of brain abnormalities in mastocytosis.

PubMed

Boddaert, N; Salvador, A; Chandesris, M O; Lemaître, H; Grévent, D; Gauthier, C; Naggara, O; Georgin-Lavialle, S; Moura, D S; Munsch, F; Jaafari, N; Zilbovicius, M; Lortholary, O; Gaillard, R; Hermine, O

2017-08-08

Mastocytosis is a rare disease in which chronic symptoms are related to mast cell accumulation and activation. Patients can display depression-anxiety-like symptoms and cognitive impairment. The pathophysiology of these symptoms may be associated with tissular mast cell infiltration, mast cell mediator release or both. The objective of this study is to perform morphological or functional brain analyses in mastocytosis to identify brain changes associated with this mast cell disorder. We performed a prospective and monocentric comparative study to evaluate the link between subjective psycho-cognitive complaints, psychiatric evaluation and objective medical data using magnetic resonance imaging with morphological and perfusion sequences (arterial spin-labeled perfusion) in 39 patients with mastocytosis compared with 33 healthy controls. In the test cohort of 39 mastocytosis patients with psycho-cognitive complaints, we found that 49% of them had morphological brain abnormalities, mainly abnormal punctuated white matter abnormalities (WMA). WMA were equally frequent in cutaneous mastocytosis patients and indolent forms of systemic mastocytosis patients (42% and 41% of patients with WMA, respectively). Patients with WMA showed increased perfusion in the putamen compared with patients without WMA and with healthy controls. Putamen perfusion was also negatively correlated with depression subscores. This study demonstrates, for we believe the first time, a high prevalence of morphological and functional abnormalities in the brains of mastocytosis patients with neuropsychiatric complaints. Further studies are required to determine the mechanism underpinning this association and to ascertain its specificity.

Fetal Alcohol Spectrum Disorders: An Overview from the Glia Perspective.

PubMed

Wilhelm, Clare J; Guizzetti, Marina

2015-01-01

Alcohol consumption during pregnancy can produce a variety of central nervous system (CNS) abnormalities in the offspring resulting in a broad spectrum of cognitive and behavioral impairments that constitute the most severe and long-lasting effects observed in fetal alcohol spectrum disorders (FASD). Alcohol-induced abnormalities in glial cells have been suspected of contributing to the adverse effects of alcohol on the developing brain for several years, although much research still needs to be done to causally link the effects of alcohol on specific brain structures and behavior to alterations in glial cell development and function. Damage to radial glia due to prenatal alcohol exposure may underlie observations of abnormal neuronal and glial migration in humans with Fetal Alcohol Syndrome (FAS), as well as primate and rodent models of FAS. A reduction in cell number and altered development has been reported for several glial cell types in animal models of FAS. In utero alcohol exposure can cause microencephaly when alcohol exposure occurs during the brain growth spurt a period characterized by rapid astrocyte proliferation and maturation; since astrocytes are the most abundant cells in the brain, microenchephaly may be caused by reduced astrocyte proliferation or survival, as observed in in vitro and in vivo studies. Delayed oligodendrocyte development and increased oligodendrocyte precursor apoptosis has also been reported in experimental models of FASD, which may be linked to altered myelination/white matter integrity found in FASD children. Children with FAS exhibit hypoplasia of the corpus callosum and anterior commissure, two areas requiring guidance from glial cells and proper maturation of oligodendrocytes. Finally, developmental alcohol exposure disrupts microglial function and induces microglial apoptosis; given the role of microglia in synaptic pruning during brain development, the effects of alcohol on microglia may be involved in the abnormal brain plasticity reported in FASD. The consequences of prenatal alcohol exposure on glial cells, including radial glia and other transient glial structures present in the developing brain, astrocytes, oligodendrocytes and their precursors, and microglia contributes to abnormal neuronal development, reduced neuron survival and disrupted brain architecture and connectivity. This review highlights the CNS structural abnormalities caused by in utero alcohol exposure and outlines which abnormalities are likely mediated by alcohol effects on glial cell development and function.

High prevalence of brain pathology in violent prisoners: a qualitative CT and MRI scan study.

PubMed

Schiltz, Kolja; Witzel, Joachim G; Bausch-Hölterhoff, Josef; Bogerts, Bernhard

2013-10-01

The aim of this study was to determine the frequency and extent of brain anomalies in a large sample of incarcerated violent offenders not previously considered neuropsychiatrically ill, in comparison with non-violent offenders and non-offending controls. MRI and CT brain scans from 287 male prison inmates (162 violent and 125 non-violent) not diagnosed as mentally ill before that were obtained due to headache, vertigo or psychological complaints during imprisonment were assessed and compared to 52 non-criminal controls. Brain scans were rated qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1) or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex and medial temporal structures bilaterally as well as third ventricle. Overall, offenders displayed a significantly higher rate of morphological abnormality, with the violent offenders scoring significantly higher than non-violent offenders and controls. This difference was statistically detectable for frontal/parietal cortex, medial temporal structures, third ventricle and the left but not the right lateral ventricle. The remarkable prevalence of brain pathology in convicted violent prisoners detectable by neuroradiological routine assessment not only highlights the importance of frontal and temporal structures in the control of social, and specifically of violent behaviour, but also raises questions on the legal culpability of violent offenders with brain abnormalities. The high proportion of undetected presence of structural brain damage emphasizes the need that in violent criminals, the comprehensive routine neuropsychiatric assessment usually performed in routine forensic psychiatric expertises should be complemented with brain imaging.

Oscillations in sensorimotor cortex in movement disorders: an electrocorticography study.

PubMed

Crowell, Andrea L; Ryapolova-Webb, Elena S; Ostrem, Jill L; Galifianakis, Nicholas B; Shimamoto, Shoichi; Lim, Daniel A; Starr, Philip A

2012-02-01

Movement disorders of basal ganglia origin may arise from abnormalities in synchronized oscillatory activity in a network that includes the basal ganglia, thalamus and motor cortices. In humans, much has been learned from the study of basal ganglia local field potentials recorded from temporarily externalized deep brain stimulator electrodes. These studies have led to the theory that Parkinson's disease has characteristic alterations in the beta frequency band (13-30 Hz) in the basal ganglia-thalamocortical network. However, different disorders have rarely been compared using recordings in the same structure under the same behavioural conditions, limiting straightforward assessment of current hypotheses. To address this, we utilized subdural electrocorticography to study cortical oscillations in the three most common movement disorders: Parkinson's disease, primary dystonia and essential tremor. We recorded local field potentials from the arm area of primary motor and sensory cortices in 31 subjects using strip electrodes placed temporarily during routine surgery for deep brain stimulator placement. We show that: (i) primary motor cortex broadband gamma power is increased in Parkinson's disease compared with the other conditions, both at rest and during a movement task; (ii) primary motor cortex high beta (20-30 Hz) power is increased in Parkinson's disease during the 'stop' phase of a movement task; (iii) the alpha-beta peaks in the motor and sensory cortical power spectra occur at higher frequencies in Parkinson's disease than in the other two disorders; and (iv) patients with dystonia have impaired movement-related beta band desynchronization in primary motor and sensory cortices. The findings support the emerging hypothesis that disease states reflect abnormalities in synchronized oscillatory activity. This is the first study of sensorimotor cortex local field potentials in the three most common movement disorders.

Genetics Home Reference: Wolf-Hirschhorn syndrome

MedlinePlus

... syndrome include skin changes such as mottled or dry skin, skeletal abnormalities such as abnormal ... also cause abnormalities of the eyes, heart, genitourinary tract, and brain. A condition called ...

Local functional connectivity alterations in schizophrenia, bipolar disorder, and major depressive disorder.

PubMed

Wei, Yange; Chang, Miao; Womer, Fay Y; Zhou, Qian; Yin, Zhiyang; Wei, Shengnan; Zhou, Yifang; Jiang, Xiaowei; Yao, Xudong; Duan, Jia; Xu, Ke; Zuo, Xi-Nian; Tang, Yanqing; Wang, Fei

2018-08-15

Local functional connectivity (FC) indicates local or short-distance functional interactions and may serve as a neuroimaging marker to investigate the human brain connectome. Local FC alterations suggest a disrupted balance in the local functionality of the whole brain network and are increasingly implicated in schizophrenia (SZ), bipolar disorder (BD), and major depressive disorder (MDD). We aim to examine the similarities and differences in the local FC across SZ, BD, and MDD. In total, 537 participants (SZ, 126; BD, 97; MDD, 126; and healthy controls, 188) completed resting-state functional magnetic resonance imaging at a single site. The local FC at resting state was calculated and compared across SZ, BD, and MDD. The local FC increased across SZ, BD, and MDD within the bilateral orbital frontal cortex (OFC) and additional region in the left OFC extending to putamen and decreased in the primary visual, auditory, and motor cortices, right supplemental motor area, and bilateral thalami. There was a gradient in the extent of alterations such that SZ > BD > MDD. This cross-sectional study cannot consider medications and other clinical variables. These findings indicate a disrupted balance between network integration and segregation in SZ, BD, and MDD, including over-integration via increased local FC in the OFC and diminished segregation of neural processing with the weakening of the local FC in the primary sensory cortices and thalamus. The shared local FC abnormalities across SZ, BD, and MDD may shed new light on the potential biological mechanisms underlying these disorders. Copyright © 2018 Elsevier B.V. All rights reserved.

Implementation of magnetic resonance elastography for the investigation of traumatic brain injuries

NASA Astrophysics Data System (ADS)

Boulet, Thomas

Magnetic resonance elastography (MRE) is a potentially transformative imaging modality allowing local and non-invasive measurement of biological tissue mechanical properties. It uses a specific phase contrast MR pulse sequence to measure induced vibratory motion in soft material, from which material properties can be estimated. Compared to other imaging techniques, MRE is able to detect tissue pathology at early stages by quantifying the changes in tissue stiffness associated with diseases. In an effort to develop the technique and improve its capabilities, two inversion algorithms were written to evaluate viscoelastic properties from the measured displacements fields. The first one was based on a direct algebraic inversion of the differential equation of motion, which decouples under certain simplifying assumptions, and featured a spatio-temporal multi-directional filter. The second one relies on a finite element discretization of the governing equations to perform a direct inversion. Several applications of this technique have also been investigated, including the estimation of mechanical parameters in various gel phantoms and polymers, as well as the use of MRE as a diagnostic tools for brain disorders. In this respect, the particular interest was to investigate traumatic brain injury (TBI), a complex and diverse injury affecting 1.7 million Americans annually. The sensitivity of MRE to TBI was first assessed on excised rat brains subjected to a controlled cortical impact (CCI) injury, before execution of in vivo experiments in mice. MRE was also applied in vivo on mouse models of medulloblastoma tumors and multiple sclerosis. These studies showed the potential of MRE in mapping the brain mechanically and providing non-invasive in vivo imaging markers for neuropathology and pathogenesis of brain diseases. Furthermore, MRE can easily be translatable to clinical settings; thus, while this technique may not be used directly to diagnose different abnormalities in the brain at this time, it may be helpful to detect abnormalities, follow therapies, and trace macroscopic changes that are not seen by conventional methods with clinical relevance.

A pathophysiologic approach for subacute encephalopathy with seizures in alcoholics (SESA) syndrome.

PubMed

Choi, Jun Yong; Kwon, Jiwon; Bae, Eun-Kee

2014-09-01

Subacute encephalopathy with seizures in alcoholics (SESA) syndrome is a unique disease entity characterized by typical clinical and electroencephalographic (EEG) features in the setting of chronic alcoholism. We present two patients with distinctive serial MRI and EEG findings which suggest a clue to the underlying pathophysiologic mechanisms of SESA syndrome. Two patients with chronic alcoholism and alcoholic liver cirrhosis presented with generalized seizures and confused mental status. Brain MRI demonstrated restricted diffusion, increased T2-weighted signal intensity, and hyperperfusion in the presumed seizure focus and nearby posterior regions of the cerebral hemispheres. EEG showed periodic lateralized epileptiform discharges which were prominent in the posterior regions of the cerebral hemispheres ipsilateral to the side of brain MRI abnormalities. Even after patients clinically improved, these brain abnormalities persisted with progressive atrophic changes on follow-up brain MRI. These patients had not only the distinguishing clinical and EEG features of SESA syndrome, but also showed novel brain MRI abnormalities. These changes on MRI displayed characteristics of seizure-related changes. The posterior dominance of abnormalities on MRI and EEG suggests that the pathophysiologic mechanisms of SESA syndrome may share those of posterior reversible encephalopathy syndrome. Copyright © 2014 Elsevier Ltd. All rights reserved.

Neurochemical abnormalities in brains of renal failure patients treated by repeated hemodialysis.

PubMed

Perry, T L; Yong, V W; Kish, S J; Ito, M; Foulks, J G; Godolphin, W J; Sweeney, V P

1985-10-01

We examined autopsied brain from 10 patients with end-stage renal failure who had undergone repeated hemodialysis. Eight had classic symptoms, and two had suggestive symptoms of dialysis encephalopathy. Findings were compared with those in autopsied brain from control adults who had never been hemodialyzed. Mean gamma-aminobutyric acid (GABA) contents were significantly reduced in frontal and occipital cortex, cerebellar cortex, dentate nucleus, caudate nucleus, and medial-dorsal thalamus of the hemodialyzed patients, the reduction being greater than 40% in cerebral cortex and thalamus. Choline acetyltransferase activity was reduced by 25-35% in three cortical regions in the hemodialyzed patients. These two abnormalities were observed in the brain of each hemodialyzed patient, regardless of whether or not the patient died with unequivocal dialysis encephalopathy. Pyridoxal phosphate contents were substantially reduced in brains of the hemodialyzed patients, but metabolites of noradrenaline, 3,4-dihydroxyphenylethylamine (dopamine), and 5-hydroxytryptamine (serotonin) were present in normal amounts. Aluminum levels were abnormally high in frontal cortical gray matter in the hemodialyzed patients. Although this study does not clarify the role played by aluminum toxicity in the pathogenesis of dialysis encephalopathy, the abnormalities we found suggest the need for further neurochemical investigations in this disorder.

Cerebellar White Matter Abnormalities following Primary Blast Injury in US Military Personnel

PubMed Central

Mac Donald, Christine; Johnson, Ann; Cooper, Dana; Malone, Thomas; Sorrell, James; Shimony, Joshua; Parsons, Matthew; Snyder, Abraham; Raichle, Marcus; Fang, Raymond; Flaherty, Stephen; Russell, Michael; Brody, David L.

2013-01-01

Little is known about the effects of blast exposure on the human brain in the absence of head impact. Clinical reports, experimental animal studies, and computational modeling of blast exposure have suggested effects on the cerebellum and brainstem. In US military personnel with isolated, primary blast-related ‘mild’ traumatic brain injury and no other known insult, we found diffusion tensor MRI abnormalities consistent with cerebellar white matter injury in 3 of 4 subjects. No abnormalities in other brain regions were detected. These findings add to the evidence supporting the hypothesis that primary blast exposure contributes to brain injury in the absence of head impact and that the cerebellum may be particularly vulnerable. However, the clinical effects of these abnormalities cannot be determined with certainty; none of the subjects had ataxia or other detected evidence of cerebellar dysfunction. The details of the blast events themselves cannot be disclosed at this time, thus additional animal and computational modeling will be required to dissect the mechanisms underlying primary blast-related traumatic brain injury. Furthermore, the effects of possible subconcussive impacts and other military-related exposures cannot be determined from the data presented. Thus many aspects of topic will require further investigation. PMID:23409052

Atherosclerosis in epilepsy: its causes and implications.

PubMed

Hamed, Sherifa A

2014-12-01

Evidence from epidemiological, longitudinal, prospective, double-blinded clinical trials as well as case reports documents age-accelerated atherosclerosis with increased carotid artery intima media thickness (CA-IMT) in patients with epilepsy. These findings raise concern regarding their implications for age-accelerated cognitive and behavioral changes in midlife and risk of later age-related cognitive disorders including neurodegenerative processes such as Alzheimer's disease (AD). Chronic epilepsy, cerebral atherosclerosis, and age-related cognitive disorders including AD share many clinical manifestations (e.g. characteristic cognitive deficits), risk factors, and structural and pathological brain abnormalities. These shared risk factors include increased CA-IMT, hyperhomocysteinemia (HHcy), lipid abnormalities, weight gain and obesity, insulin resistance (IR), and high levels of inflammatory and oxidative stresses. The resulting brain structural and pathological abnormalities include decreased volume of the hippocampus, increased cortical thinning of the frontal lobe, ventricular expansion and increased white matter ischemic disease, total brain atrophy, and β-amyloid protein deposition in the brain. The knowledge that age-accelerated atherosclerosis may contribute to age-accelerated cognitive and behavioral abnormalities and structural brain pathologies in patients with chronic epilepsy represents an important research path to pursue future clinical and management considerations. Copyright © 2014 Elsevier Inc. All rights reserved.

White matter alterations in narcolepsy patients with cataplexy: tract-based spatial statistics.

PubMed

Park, Yun K; Kwon, Oh-Hun; Joo, Eun Yeon; Kim, Jae-Hun; Lee, Jong M; Kim, Sung T; Hong, Seung B

2016-04-01

Functional imaging studies and voxel-based morphometry analysis of brain magnetic resonance imaging showed abnormalities in the hypothalamus-thalamus-orbitofrontal pathway, demonstrating altered hypocretin pathway in narcolepsy. Those distinct morphometric changes account for problems in wake-sleep control, attention and memory. It also raised the necessity to evaluate white matter changes. To investigate brain white matter alterations in drug-naïve narcolepsy patients with cataplexy and to explore relationships between white matter changes and patient clinical characteristics, drug-naïve narcolepsy patients with cataplexy (n = 22) and healthy age- and gender-matched controls (n = 26) were studied. Fractional anisotropy and mean diffusivity images were obtained from whole-brain diffusion tensor imaging, and tract-based spatial statistics were used to localize white matter abnormalities. Compared with controls, patients showed significant decreases in fractional anisotropy of white matter of the bilateral anterior cingulate, fronto-orbital area, frontal lobe, anterior limb of the internal capsule and corpus callosum, as well as the left anterior and medial thalamus. Patients and controls showed no differences in mean diffusivity. Among patients, mean diffusivity values of white matter in the bilateral superior frontal gyri, bilateral fronto-orbital gyri and right superior parietal gyrus were positively correlated with depressive mood. This tract-based spatial statistics study demonstrated that drug-naïve patients with narcolepsy had reduced fractional anisotropy of white matter in multiple brain areas and significant relationship between increased mean diffusivity of white matter in frontal/cingulate and depression. It suggests the widespread disruption of white matter integrity and prevalent brain degeneration of frontal lobes according to a depressive symptom in narcolepsy. © 2015 European Sleep Research Society.

Three-dimensional brain growth abnormalities in childhood-onset schizophrenia visualized by using tensor-based morphometry.

PubMed

Gogtay, Nitin; Lu, Allen; Leow, Alex D; Klunder, Andrea D; Lee, Agatha D; Chavez, Alex; Greenstein, Deanna; Giedd, Jay N; Toga, Arthur W; Rapoport, Judith L; Thompson, Paul M

2008-10-14

Earlier studies revealed progressive cortical gray matter (GM) loss in childhood-onset schizophrenia (COS) across both lateral and medial surfaces of the developing brain. Here, we use tensor-based morphometry to visualize white matter (WM) growth abnormalities in COS throughout the brain. Using high-dimensional elastic image registration, we compared 3D maps of local WM growth rates in COS patients and healthy children over a 5-year period, based on analyzing longitudinal brain MRIs from 12 COS patients and 12 healthy controls matched for age, gender, and scan interval. COS patients showed up to 2.2% slower growth rates per year than healthy controls in WM (P = 0.02, all P values corrected). The greatest differences were in the right hemisphere (P = 0.006). This asymmetry was attributable to a right slower than left hemisphere growth rate mapped in COS patients (P = 0.037) but not in healthy controls. WM growth rates reached 2.6% per year in healthy controls (P = 0.0002). COS patients showed only a 1.3% per year trend for growth in the left hemisphere (P = 0.066). In COS, WM growth rates were associated with improvement in the Children's Global Assessment Scale (R = 0.64, P = 0.029). Growth rates were reduced throughout the brain in COS, but this process appeared to progress in a front-to-back (frontal-parietal) fashion, and this effect was not attributable to lower IQ. Growth rates were correlated with functional prognosis and were visualized as detailed 3D maps. Finally, these findings also confirm that the progressive GM deficits seen in schizophrenia are not the result of WM overgrowth.

Alterations of local cerebral glucose utilization in lean and obese fa/fa rats after acute adrenalectomy.

PubMed

Doyle, P; Rohner-Jeanrenaud, F; Jeanrenaud, B

1994-08-29

An animal model often used to investigate the aetiology of obesity is the genetically obese fa/fa rat. It has many abnormalities, including hyperphagia, hyper-insulinemia, insulin resistance, low cerebral glucose utilization and an overactive hypothalamo-pituitary adrenal (HPA) axis with resulting hypercorticism. Due to the latter consideration, the aim of this work was to study the impact of acute adrenalectomy (ADX) on the local cerebral glucose utilization (LCGU) of lean and obese fa/fa rats. ADX resulted in discrete increases in LCGU of regions common to both lean and obese rats. These common regions were found to belong to be related to the limbic system. Within this system, the LCGU of the brain of obese rats was either normalized to lean sham operated values or increased by ADX to a similar degree in both groups on a percentage basis. It was concluded that the LCGU of both lean and obese animals appears to be negatively regulated, albeit to different extents, by glucocorticoids. Such negative regulation is particularly salient within the limbic system of the lean rat and even more so in the fa/fa rat. It is suggested that the long-term hypercorticism of obese fa/fa rats due to abnormal regulation of the HPA axis may result in a decreased LCGU in limbic and related regions of the brain of fa/fa rats and contribute to the expression of the obese phenotype.

NORADRENERGIC CONTROL OF CORTICO-STRIATO-THALAMIC AND MESOLIMBIC CROSS-STRUCTURAL SYNCHRONY

PubMed Central

Dzirasa, Kafui; Phillips, H. Westley; Sotnikova, Tatyana D.; Salahpour, Ali; Kumar, Sunil; Gainetdinov, Raul R.; Caron, Marc G.; Nicolelis, Miguel A. L.

2010-01-01

While normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials (LFPs) and single neuron activity across ten interconnected brain areas (ventral striatum, frontal association cortex hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits, and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute twelve-fold increase in grooming. Notably, treatment with a norepinephrine precursors (L-DOPA 100mg/kg or L-DOPS 5mg/kg), or a selective serotonin reuptake inhibitor (fluoxetine 20mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striatal-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors. PMID:20445065

Noradrenergic control of cortico-striato-thalamic and mesolimbic cross-structural synchrony.

PubMed

Dzirasa, Kafui; Phillips, H Westley; Sotnikova, Tatyana D; Salahpour, Ali; Kumar, Sunil; Gainetdinov, Raul R; Caron, Marc G; Nicolelis, Miguel A L

2010-05-05

Although normal dopaminergic tone has been shown to be essential for the induction of cortico-striatal and mesolimbic theta oscillatory activity, the influence of norepinephrine on these brain networks remains relatively unknown. To address this question, we simultaneously recorded local field potentials and single-neuron activity across 10 interconnected brain areas (ventral striatum, frontal association cortex, hippocampus, primary motor cortex, orbital frontal cortex, prelimbic cortex, dorsal lateral striatum, medial dorsal nucleus of thalamus, substantia nigra pars reticularis, and ventral tegmental area) in a combined genetically and pharmacologically induced mouse model of hyponoradrenergia. Our results show that norepinephrine (NE) depletion induces a novel state in male mice characterized by a profound disruption of coherence across multiple cortico-striatal circuits and an increase in mesolimbic cross-structural coherence. Moreover, this brain state is accompanied by a complex behavioral phenotype consisting of transient hyperactivity, stereotypic behaviors, and an acute 12-fold increase in grooming. Notably, treatment with a norepinephrine precursors (l-3,4-dihydroxyphenylalanine at 100 mg/kg or l-threo-dihydroxyphenylserine at 5 mg/kg) or a selective serotonin reuptake inhibitor (fluoxetine at 20 mg/kg) attenuates the abnormal behaviors and selectively reverses the circuit changes observed in NE-depleted mice. Together, our results demonstrate that norepinephrine modulates the dynamic tuning of coherence across cortico-striato-thalamic circuits, and they suggest that changes in coherence across these circuits mediate the abnormal generation of hyperactivity and repetitive behaviors.

Comparison of gray matter volume and thickness for analysis of cortical changes in Alzheimer's disease

NASA Astrophysics Data System (ADS)

Liu, Jiachao; Li, Ziyi; Chen, Kewei; Yao, Li; Wang, Zhiqun; Li, Kunchen; Guo, Xiaojuan

2011-03-01

Gray matter volume and cortical thickness are two indices of concern in brain structure magnetic resonance imaging research. Gray matter volume reflects mixed-measurement information of cerebral cortex, while cortical thickness reflects only the information of distance between inner surface and outer surface of cerebral cortex. Using Scaled Subprofile Modeling based on Principal Component Analysis (SSM_PCA) and Pearson's Correlation Analysis, this study further provided quantitative comparisons and depicted both global relevance and local relevance to comprehensively investigate morphometrical abnormalities in cerebral cortex in Alzheimer's disease (AD). Thirteen patients with AD and thirteen age- and gender-matched healthy controls were included in this study. Results showed that factor scores from the first 8 principal components accounted for ~53.38% of the total variance for gray matter volume, and ~50.18% for cortical thickness. Factor scores from the fifth principal component showed significant correlation. In addition, gray matter voxel-based volume was closely related to cortical thickness alterations in most cortical cortex, especially, in some typical abnormal brain regions such as insula and the parahippocampal gyrus in AD. These findings suggest that these two measurements are effective indices for understanding the neuropathology in AD. Studies using both gray matter volume and cortical thickness can separate the causes of the discrepancy, provide complementary information and carry out a comprehensive description of the morphological changes of brain structure.

Resting state functional MRI reveals abnormal network connectivity in neurofibromatosis 1.

PubMed

Tomson, Steffie N; Schreiner, Matthew J; Narayan, Manjari; Rosser, Tena; Enrique, Nicole; Silva, Alcino J; Allen, Genevera I; Bookheimer, Susan Y; Bearden, Carrie E

2015-11-01

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits, and autism spectrum disorders. As a single-gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity magnetic resonance imaging (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. © 2015 Wiley Periodicals, Inc.

Resting state functional MRI reveals abnormal network connectivity in Neurofibromatosis 1

PubMed Central

Tomson, S.N.; Schreiner, M.; Narayan, M.; Rosser, Tena; Enrique, Nicole; Silva, Alcino J.; Allen, G.I.; Bookheimer, S.Y.; Bearden, C.E.

2015-01-01

Neurofibromatosis type I (NF1) is a genetic disorder caused by mutations in the neurofibromin 1 gene at locus 17q11.2. Individuals with NF1 have an increased incidence of learning disabilities, attention deficits and autism spectrum disorders. As a single gene disorder, NF1 represents a valuable model for understanding gene-brain-behavior relationships. While mouse models have elucidated molecular and cellular mechanisms underlying learning deficits associated with this mutation, little is known about functional brain architecture in human subjects with NF1. To address this question, we used resting state functional connectivity MRI (rs-fcMRI) to elucidate the intrinsic network structure of 30 NF1 participants compared with 30 healthy demographically matched controls during an eyes-open rs-fcMRI scan. Novel statistical methods were employed to quantify differences in local connectivity (edge strength) and modularity structure, in combination with traditional global graph theory applications. Our findings suggest that individuals with NF1 have reduced anterior-posterior connectivity, weaker bilateral edges, and altered modularity clustering relative to healthy controls. Further, edge strength and modular clustering indices were correlated with IQ and internalizing symptoms. These findings suggest that Ras signaling disruption may lead to abnormal functional brain connectivity; further investigation into the functional consequences of these alterations in both humans and in animal models is warranted. PMID:26304096

A family affair: brain abnormalities in siblings of patients with schizophrenia.

PubMed

Moran, Marcel E; Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-11-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development.

A family affair: brain abnormalities in siblings of patients with schizophrenia

PubMed Central

Hulshoff Pol, Hilleke; Gogtay, Nitin

2013-01-01

Schizophrenia is a severe mental disorder that has a strong genetic basis. Converging evidence suggests that schizophrenia is a progressive neurodevelopmental disorder, with earlier onset cases resulting in more profound brain abnormalities. Siblings of patients with schizophrenia provide an invaluable resource for differentiating between trait and state markers, thus highlighting possible endophenotypes for ongoing research. However, findings from sibling studies have not been systematically put together in a coherent story across the broader age span. We review here the cortical grey matter abnormalities in siblings of patients with schizophrenia from childhood to adulthood, by reviewing sibling studies from both childhood-onset schizophrenia, and the more common adult-onset schizophrenia. When reviewed together, studies suggest that siblings of patients with schizophrenia display significant brain abnormalities that highlight both similarities and differences between the adult and childhood populations, with shared developmental risk patterns, and segregating trajectories. Based on current research it appears that the cortical grey matter abnormalities in siblings are likely to be an age-dependent endophenotype, which normalize by the typical age of onset of schizophrenia unless there has been more genetic or symptom burdening. With increased genetic burdening (e.g. discordant twins of patients) the grey matter abnormalities in (twin) siblings are progressive in adulthood. This synthesis of the literature clarifies the importance of brain plasticity in the pathophysiology of the illness, indicating that probands may lack protective factors critical for healthy development. PMID:23698280

In vivo biocompatibility and in vitro characterization of poly-lactide-co-glycolide structures containing levetiracetam, for the treatment of epilepsy.

PubMed

Halliday, Amy J; Campbell, Toni E; Razal, Joselito M; McLean, Karen J; Nelson, Timothy S; Cook, Mark J; Wallace, Gordon G

2012-02-01

Epilepsy is a chronic neurological disorder characterized by recurrent seizures, and is highly resistant to medication with up to 40% of patients continuing to experience seizures whilst taking oral antiepileptic drugs. Recent research suggests that this may be due to abnormalities in the blood-brain barrier, which prevent the passage of therapeutic substances into the brain. We sought to develop a drug delivery material that could be implanted within the brain at the origin of the seizures to release antiepileptic drugs locally and avoid the blood brain barrier. We produced poly-lactide-co-glycolide drop-cast films and wet-spun fibers loaded with the novel antiepileptic drug Levetiracetam, and investigated their morphology, in vitro drug release characteristics, and brain biocompatibility in adult rats. The best performing structures released Levetiracetam constantly for at least 5 months in vitro, and were found to be highly brain biocompatible following month-long implantations in the motor cortex of adult rats. These results demonstrate the potential of polymer-based drug delivery devices in the treatment of epilepsy and warrant their investigation in animal models of focal epilepsy. Copyright © 2011 Wiley Periodicals, Inc.

Types of traumatic brain injury and regional cerebral blood flow assessed by 99mTc-HMPAO SPECT.

PubMed

Yamakami, I; Yamaura, A; Isobe, K

1993-01-01

To investigate the relationship between focal and diffuse traumatic brain injury (TBI) and regional cerebral blood flow (rCBF), rCBF changes in the first 24 hours post-trauma were studied in 12 severe head trauma patients using single photon emission computed tomography (SPECT) with 99mtechnetium-hexamethyl propyleneamine oxime. Patients were classified as focal or diffuse TBI based on x-ray computed tomographic (X-CT) findings and neurological signs. In six patients with focal damage, SPECT demonstrated 1) perfusion defect (focal severe ischemia) in the brain region larger than the brain contusion by X-CT, 2) hypoperfusion (focal CBF reduction) in the brain region without abnormality by X-CT, and 3) localized hyperperfusion (focal CBF increase) in the surgically decompressed brain after decompressive craniectomy. Focal damage may be associated with a heterogeneous CBF change by causing various focal CBF derangements. In six patients with diffuse damage, SPECT revealed hypoperfusion in only one patient. Diffuse damage may be associated with a homogeneous CBF change by rarely causing focal CBF derangements. The type of TBI, focal or diffuse, determines the type of CBF change, heterogeneous or homogeneous, in the acute severe head trauma patient.

Brain imaging in normal kids: a community-based MRI study in Malawian children.

PubMed

Potchen, M J; Kampondeni, S D; Mallewa, M; Taylor, T E; Birbeck, G L

2013-04-01

To collect normative MRI data for effective clinical and research applications. Such data may also offer insights into common neurological insults. We identified a representative, community-based sample of children aged 9-14 years. Children were screened for neurodevelopmental problems. Demographic data, medical history and environmental exposures were ascertained. Eligible children underwent the Neurologic Examination for Subtle Signs (NESS) and a brain MRI. Descriptive findings and analyses to identify risk factors for MRI abnormalities are detailed. One hundred and two of 170 households screened had age-appropriate children. Two of 102 children had neurological problems - one each with cerebral palsy and epilepsy. Ninety-six of 100 eligible children were enrolled. Mean age was 11.9 years (SD 1.5), and 43 (45%) were boys. No acute MRI abnormalities were seen. NESS abnormalities were identified in 6 of 96 children (6%). Radiographic evidence of sinusitis in 29 children (30%) was the most common MRI finding. Brain abnormalities were found in 16 (23%): mild diffuse atrophy in 4 (4%), periventricular white matter changes/gliosis in 6 (6%), multifocal punctuate subcortical white matter changes in 2 (2%), vermian atrophy in 1 (1%), empty sella in 3 (3%) and multifocal granulomas with surrounding gliosis in 1 (1%). Having an abnormal MRI was not associated with age, sex, antenatal problems, early malnutrition, febrile seizures, an abnormal neurological examination or housing quality (all P values >0.05). No predictors of radiographic sinusitis were identified. Incidental brain MRI abnormalities are common in normal Malawian children. The incidental atrophy and white matter abnormalities seen in this African population have not been reported among incidental findings from US populations, suggesting Malawi-specific exposures may be the cause. © 2013 Blackwell Publishing Ltd.

Periventricular Nodular Heterotopia: Detection of Abnormal Microanatomic Fiber Structures with Whole-Brain Diffusion MR Imaging Tractography.

PubMed

Farquharson, Shawna; Tournier, J-Donald; Calamante, Fernando; Mandelstam, Simone; Burgess, Rosemary; Schneider, Michal E; Berkovic, Samuel F; Scheffer, Ingrid E; Jackson, Graeme D; Connelly, Alan

2016-12-01

Purpose To investigate whether it is possible in patients with periventricular nodular heterotopia (PVNH) to detect abnormal fiber projections that have only previously been reported in the histopathology literature. Materials and Methods Whole-brain diffusion-weighted (DW) imaging data from 14 patients with bilateral PVNH and 14 age- and sex-matched healthy control subjects were prospectively acquired by using 3.0-T magnetic resonance (MR) imaging between August 1, 2008, and December 5, 2012. All participants provided written informed consent. The DW imaging data were processed to generate whole-brain constrained spherical deconvolution (CSD)-based tractography data and super-resolution track-density imaging (TDI) maps. The tractography data were overlaid on coregistered three-dimensional T1-weighted images to visually assess regions of heterotopia. A panel of MR imaging researchers independently assessed each case and indicated numerically (no = 1, yes = 2) as to the presence of abnormal fiber tracks in nodular tissue. The Fleiss κ statistical measure was applied to assess the reader agreement. Results Abnormal fiber tracks emanating from one or more regions of heterotopia were reported by all four readers in all 14 patients with PVNH (Fleiss κ = 1). These abnormal structures were not visible on the tractography data from any of the control subjects and were not discernable on the conventional T1-weighted images of the patients with PVNH. Conclusion Whole-brain CSD-based fiber tractography and super-resolution TDI mapping reveals abnormal fiber projections in nodular tissue suggestive of abnormal organization of white matter (with abnormal fibers both within nodules and projecting to the surrounding white matter) in patients with bilateral PVNH. © RSNA, 2016.

New MR imaging assessment tool to define brain abnormalities in very preterm infants at term.

PubMed

Kidokoro, H; Neil, J J; Inder, T E

2013-01-01

WM injury is the dominant form of injury in preterm infants. However, other cerebral structures, including the deep gray matter and the cerebellum, can also be affected by injury and/or impaired growth. Current MR imaging injury assessment scales are subjective and are challenging to apply. Thus, we developed a new assessment tool and applied it to MR imaging studies obtained from very preterm infants at term age. MR imaging scans from 97 very preterm infants (< 30 weeks' gestation) and 22 healthy term-born infants were evaluated retrospectively. The severity of brain injury (defined by signal abnormalities) and impaired brain growth (defined with biometrics) was scored in the WM, cortical gray matter, deep gray matter, and cerebellum. Perinatal variables for clinical risks were collected. In very preterm infants, brain injury was observed in the WM (n=23), deep GM (n=5), and cerebellum (n=23). Combining measures of injury and impaired growth showed moderate to severe abnormalities most commonly in the WM (n=38) and cerebellum (n=32) but still notable in the cortical gray matter (n=16) and deep gray matter (n=11). WM signal abnormalities were associated with a reduced deep gray matter area but not with cerebellar abnormality. Intraventricular and/or parenchymal hemorrhage was associated with cerebellar signal abnormality and volume reduction. Multiple clinical risk factors, including prolonged intubation, prolonged parenteral nutrition, postnatal corticosteroid use, and postnatal sepsis, were associated with increased global abnormality on MR imaging. Very preterm infants demonstrate a high prevalence of injury and growth impairment in both the WM and gray matter. This MR imaging scoring system provides a more comprehensive and objective classification of the nature and extent of abnormalities than existing measures.

Correlations between ventricular enlargement and gray and white matter volumes of cortex, thalamus, striatum, and internal capsule in schizophrenia.

PubMed

Horga, Guillermo; Bernacer, Javier; Dusi, Nicola; Entis, Jonathan; Chu, Kingwai; Hazlett, Erin A; Haznedar, M Mehmet; Kemether, Eileen; Byne, William; Buchsbaum, Monte S

2011-10-01

Ventricular enlargement is one of the most consistent abnormal structural brain findings in schizophrenia and has been used to infer brain shrinkage. However, whether ventricular enlargement is related to local overlying cortex and/or adjacent subcortical structures or whether it is related to brain volume change globally has not been assessed. We systematically assessed interrelations of ventricular volumes with gray and white matter volumes of 40 Brodmann areas (BAs), the thalamus and its medial dorsal nucleus and pulvinar, the internal capsule, caudate and putamen. We acquired structural MRI ( patients with schizophrenia (n = 64) and healthy controls (n = 56)) and diffusion tensor fractional anisotropy (FA) (untreated schizophrenia n = 19, controls n = 32). Volumes were assessed by manual tracing of central structures and a semi-automated parcellation of BAs. Patients with schizophrenia had increased ventricular size associated with decreased cortical gray matter volumes widely across the brain; a similar but less pronounced pattern was seen in normal controls; local correlations (e.g. temporal horn with temporal lobe volume) were not appreciably higher than non-local correlations (e.g. temporal horn with prefrontal volume). White matter regions adjacent to the ventricles similarly did not reveal strong regional relationships. FA and center of mass of the anterior limb of the internal capsule also appeared differentially influenced by ventricular volume but findings were similarly not regional. Taken together, these findings indicate that ventricular enlargement is globally interrelated with gray matter volume diminution but not directly correlated with volume loss in the immediately adjacent caudate, putamen, or internal capsule.

Blood-Brain Barrier Breakdown Following Traumatic Brain Injury: A Possible Role in Posttraumatic Epilepsy

PubMed Central

Tomkins, Oren; Feintuch, Akiva; Benifla, Moni; Cohen, Avi; Friedman, Alon; Shelef, Ilan

2011-01-01

Recent animal experiments indicate a critical role for opening of the blood-brain barrier (BBB) in the pathogenesis of post-traumatic epilepsy (PTE). This study aimed to investigate the frequency, extent, and functional correlates of BBB disruption in epileptic patients following mild traumatic brain injury (TBI). Thirty-seven TBI patients were included in this study, 19 of whom suffered from PTE. All underwent electroencephalographic (EEG) recordings and brain magnetic resonance imaging (bMRI). bMRIs were evaluated for BBB disruption using novel quantitative techniques. Cortical dysfunction was localized using standardized low-resolution brain electromagnetic tomography (sLORETA). TBI patients displayed significant EEG slowing compared to controls with no significant differences between PTE and nonepileptic patients. BBB disruption was found in 82.4% of PTE compared to 25% of non-epileptic patients (P = .001) and could be observed even years following the trauma. The volume of cerebral cortex with BBB disruption was significantly larger in PTE patients (P = .001). Slow wave EEG activity was localized to the same region of BBB disruption in 70% of patients and correlated to the volume of BBB disrupted cortex. We finally present a patient suffering from early cortical dysfunction and BBB breakdown with a gradual and parallel resolution of both pathologies. Our findings demonstrate that BBB pathology is frequently found following mild TBI. Lasting BBB breakdown is found with increased frequency and extent in PTE patients. Based on recent animal studies and the colocalization found between the region of disrupted BBB and abnormal EEG activity, we suggest a role for a vascular lesion in the pathogenesis of PTE. PMID:21436875

Functional and structural brain correlates of theory of mind and empathy deficits in schizophrenia.

PubMed

Benedetti, Francesco; Bernasconi, Alessandro; Bosia, Marta; Cavallaro, Roberto; Dallaspezia, Sara; Falini, Andrea; Poletti, Sara; Radaelli, Daniele; Riccaboni, Roberta; Scotti, Giuseppe; Smeraldi, Enrico

2009-10-01

Patients affected by schizophrenia show deficits in social cognition, with abnormal performance on tasks targeting theory of mind (ToM) and empathy (Emp). Brain imaging studies suggested that ToM and Emp depend on the activation of brain networks mainly localized at the superior temporal lobe and temporo-parietal junction. Participants included 24 schizophrenia patients and 20 control subjects. We used brain blood oxygen level dependent fMRI to study the neural responses to tasks targeting ToM and Emp. We then studied voxel-based morphometry of grey matter in areas where diagnosis influenced functional activation to both tasks. Outcomes were analyzed in the context of the general linear model, with global grey matter volume as nuisance covariate for structural MRI. Patients showed worse performance on both tasks. We found significant effects of diagnosis on neural responses to the tasks in a wide cluster in right posterior superior temporal lobe (encompassing BA 22-42), in smaller clusters in left temporo-parietal junction and temporal pole (BA 38 and 39), and in a white matter region adjacent to medial prefrontal cortex (BA 10). A pattern of double dissociation of the effects of diagnosis and task on neural responses emerged. Among these areas, grey matter volume was found to be reduced in right superior temporal lobe regions of patients. Functional and structural abnormalities were observed in areas affected by the schizophrenic process early in the illness course, and known to be crucial for social cognition, suggesting a biological basis for social cognition deficits in schizophrenia.

The autistic brain in the context of normal neurodevelopment.

PubMed

Ziats, Mark N; Edmonson, Catherine; Rennert, Owen M

2015-01-01

The etiology of autism spectrum disorders (ASDs) is complex and largely unclear. Among various lines of inquiry, many have suggested convergence onto disruptions in both neural circuitry and immune regulation/glial cell function pathways. However, the interpretation of the relationship between these two putative mechanisms has largely focused on the role of exogenous factors and insults, such as maternal infection, in activating immune pathways that in turn result in neural network abnormalities. Yet, given recent insights into our understanding of human neurodevelopment, and in particular the critical role of glia and the immune system in normal brain development, it is important to consider these putative pathological processes in their appropriate normal neurodevelopmental context. In this review, we explore the hypothesis that the autistic brain cellular phenotype likely represents intrinsic abnormalities of glial/immune processes constitutively operant in normal brain development that result in the observed neural network dysfunction. We review recent studies demonstrating the intercalated role of neural circuit development, the immune system, and glial cells in the normal developing brain, and integrate them with studies demonstrating pathological alterations in these processes in autism. By discussing known abnormalities in the autistic brain in the context of normal brain development, we explore the hypothesis that the glial/immune component of ASD may instead be related to intrinsic exaggerated/abnormal constitutive neurodevelopmental processes such as network pruning. Moreover, this hypothesis may be relevant to other neurodevelopmental disorders that share genetic, pathologic, and clinical features with autism.

Machine learning classifier using abnormal brain network topological metrics in major depressive disorder.

PubMed

Guo, Hao; Cao, Xiaohua; Liu, Zhifen; Li, Haifang; Chen, Junjie; Zhang, Kerang

2012-12-05

Resting state functional brain networks have been widely studied in brain disease research. However, it is currently unclear whether abnormal resting state functional brain network metrics can be used with machine learning for the classification of brain diseases. Resting state functional brain networks were constructed for 28 healthy controls and 38 major depressive disorder patients by thresholding partial correlation matrices of 90 regions. Three nodal metrics were calculated using graph theory-based approaches. Nonparametric permutation tests were then used for group comparisons of topological metrics, which were used as classified features in six different algorithms. We used statistical significance as the threshold for selecting features and measured the accuracies of six classifiers with different number of features. A sensitivity analysis method was used to evaluate the importance of different features. The result indicated that some of the regions exhibited significantly abnormal nodal centralities, including the limbic system, basal ganglia, medial temporal, and prefrontal regions. Support vector machine with radial basis kernel function algorithm and neural network algorithm exhibited the highest average accuracy (79.27 and 78.22%, respectively) with 28 features (P<0.05). Correlation analysis between feature importance and the statistical significance of metrics was investigated, and the results revealed a strong positive correlation between them. Overall, the current study demonstrated that major depressive disorder is associated with abnormal functional brain network topological metrics and statistically significant nodal metrics can be successfully used for feature selection in classification algorithms.

Detecting subject-specific activations using fuzzy clustering

PubMed Central

Seghier, Mohamed L.; Friston, Karl J.; Price, Cathy J.

2007-01-01

Inter-subject variability in evoked brain responses is attracting attention because it may reflect important variability in structure–function relationships over subjects. This variability could be a signature of degenerate (many-to-one) structure–function mappings in normal subjects or reflect changes that are disclosed by brain damage. In this paper, we describe a non-iterative fuzzy clustering algorithm (FCP: fuzzy clustering with fixed prototypes) for characterizing inter-subject variability in between-subject or second-level analyses of fMRI data. The approach identifies the contribution of each subject to response profiles in voxels surviving a classical F-statistic criterion. The output identifies subjects who drive activation in specific cortical regions (local effects) or in voxels distributed across neural systems (global effects). The sensitivity of the approach was assessed in 38 normal subjects performing an overt naming task. FCP revealed that several subjects had either abnormally high or abnormally low responses. FCP may be particularly useful for characterizing outlier responses in rare patients or heterogeneous populations. In these cases, atypical activations may not be detected by standard tests, under parametric assumptions. The advantage of using FCP is that it searches all voxels systematically and can identify atypical activation patterns in a quantitative and unsupervised manner. PMID:17478103

Neuroimaging Findings from Childhood Onset Schizophrenia Patients and their Non-Psychotic Siblings

PubMed Central

Ordóñez, Anna E.; Luscher, Zoe; Gogtay, Nitin

2015-01-01

Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia. PMID:25819937

Neuroimaging findings from childhood onset schizophrenia patients and their non-psychotic siblings.

PubMed

Ordóñez, Anna E; Luscher, Zoe I; Gogtay, Nitin

2016-06-01

Childhood onset schizophrenia (COS), with onset of psychosis before age 13, is a rare form of schizophrenia that represents a more severe and chronic form of the adult onset illness. In this review we examine structural and functional magnetic resonance imaging (MRI) studies of COS and non-psychotic siblings of COS patients in the context of studies of schizophrenia as a whole. Studies of COS to date reveal progressive loss of gray matter volume and cortical thinning, ventricular enlargement, progressive decline in cerebellar volume and a significant but fixed deficit in hippocampal volume. COS is also associated with a slower rate of white matter growth and disrupted local connectivity strength. Sibling studies indicate that non-psychotic siblings of COS patients share many of these brain abnormalities, including decreased cortical thickness and disrupted white matter growth, yet these abnormalities normalize with age. Cross-sectional and longitudinal neuroimaging studies remain some of the few methods for assessing human brain function and play a pivotal role in the quest for understanding the neurobiology of schizophrenia as well as other psychiatric disorders. Parallel studies in non-psychotic siblings provide a unique opportunity to understand both risk and resilience in schizophrenia. Published by Elsevier B.V.

Introduction to the special section: Myelin and oligodendrocyte abnormalities in schizophrenia.

PubMed

Haroutunian, Vahram; Davis, Kenneth L

2007-08-01

A central tenet of modern views of the neurobiology of schizophrenia is that the symptoms of schizophrenia arise from a failure of adequate communication between different brain regions and disruption of the circuitry that underlies behaviour and perception. Historically this disconnectivity syndrome has been approached from a neurotransmitter-based perspective. However, efficient communication between brain circuits is also contingent on saltatory signal propagation and salubrious myelination of axons. The papers in this Special Section examine the neuroanatomical and molecular biological evidence for abnormal myelination and oligodendroglial function in schizophrenia through studies of post-mortem brain tissue and animal model systems. The picture that emerges from the studies described suggests that although schizophrenia is not characterized by gross abnormalities of white matter such as those evident in multiple sclerosis, it does involve a profound dysregulation of myelin-associated gene expression, reductions in oligodendrocyte numbers, and marked abnormalities in the ultrastructure of myelin sheaths.

Primary Cortical Folding in the Human Newborn: An Early Marker of Later Functional Development

ERIC Educational Resources Information Center

Dubois, J.; Benders, M.; Borradori-Tolsa, C.; Cachia, A.; Lazeyras, F.; Leuchter, R. Ha-Vinh; Sizonenko, S. V.; Warfield, S. K.; Mangin, J. F.; Huppi, P. S.

2008-01-01

In the human brain, the morphology of cortical gyri and sulci is complex and variable among individuals, and it may reflect pathological functioning with specific abnormalities observed in certain developmental and neuropsychiatric disorders. Since cortical folding occurs early during brain development, these structural abnormalities might be…

The functional connectome of cognitive reserve

PubMed Central

Marques, Paulo; Moreira, Pedro; Magalhães, Ricardo; Costa, Patrício; Santos, Nadine; Zihl, Josef; Soares, José

2016-01-01

Abstract Cognitive Reserve (CR) designates the brain's capacity to actively cope with insults through a more efficient use of its resources/networks. It was proposed in order to explain the discrepancies between the observed cognitive ability and the expected capacity for an individual. Typical proxies of CR include education and Intelligence Quotient but none totally account for the variability of CR and no study has shown if the brain's greater efficiency associated with CR can be measured. We used a validated model to estimate CR from the residual variance in memory and general executive functioning, accounting for both brain anatomical (i.e., gray matter and white matter signal abnormalities volume) and demographic variables (i.e., years of formal education and sex). Functional connectivity (FC) networks and topological properties were explored for associations with CR. Demographic characteristics, mainly accounted by years of formal education, were associated with higher FC, clustering, local efficiency and strength in parietal and occipital regions and greater network transitivity. Higher CR was associated with a greater FC, local efficiency and clustering of occipital regions, strength and centrality of the inferior temporal gyrus and higher global efficiency. Altogether, these findings suggest that education may facilitate the brain's ability to form segregated functional groups, reinforcing the view that higher education level triggers more specialized use of neural processing. Additionally, this study demonstrated for the first time that CR is associated with more efficient processing of information in the human brain and reinforces the existence of a fine balance between segregation and integration. Hum Brain Mapp 37:3310–3322, 2016.. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. PMID:27144904

Detection of Blast-Related Traumatic Brain Injury in U.S. Military Personnel

PubMed Central

Mac Donald, Christine L.; Johnson, Ann M.; Cooper, Dana; Nelson, Elliot C.; Werner, Nicole J.; Shimony, Joshua S.; Snyder, Abraham Z.; Raichle, Marcus E.; Witherow, John R.; Fang, Raymond; Flaherty, Stephen F.; Brody, David L.

2011-01-01

BACKGROUND Blast-related traumatic brain injuries have been common in the Iraq and Afghanistan wars, but fundamental questions about the nature of these injuries remain unanswered. METHODS We tested the hypothesis that blast-related traumatic brain injury causes traumatic axonal injury, using diffusion tensor imaging (DTI), an advanced form of magnetic resonance imaging that is sensitive to axonal injury. The subjects were 63 U.S. military personnel who had a clinical diagnosis of mild, uncomplicated traumatic brain injury. They were evacuated from the field to the Landstuhl Regional Medical Center in Landstuhl, Germany, where they underwent DTI scanning within 90 days after the injury. All the subjects had primary blast exposure plus another, blast-related mechanism of injury (e.g., being struck by a blunt object or injured in a fall or motor vehicle crash). Controls consisted of 21 military personnel who had blast exposure and other injuries but no clinical diagnosis of traumatic brain injury. RESULTS Abnormalities revealed on DTI were consistent with traumatic axonal injury in many of the subjects with traumatic brain injury. None had detectible intracranial injury on computed tomography. As compared with DTI scans in controls, the scans in the subjects with traumatic brain injury showed marked abnormalities in the middle cerebellar peduncles (P<0.001), in cingulum bundles (P = 0.002), and in the right orbitofrontal white matter (P = 0.007). In 18 of the 63 subjects with traumatic brain injury, a significantly greater number of abnormalities were found on DTI than would be expected by chance (P<0.001). Follow-up DTI scans in 47 subjects with traumatic brain injury 6 to 12 months after enrollment showed persistent abnormalities that were consistent with evolving injuries. CONCLUSIONS DTI findings in U.S. military personnel support the hypothesis that blast-related mild traumatic brain injury can involve axonal injury. However, the contribution of primary blast exposure as compared with that of other types of injury could not be determined directly, since none of the subjects with traumatic brain injury had isolated primary blast injury. Furthermore, many of these subjects did not have abnormalities on DTI. Thus, traumatic brain injury remains a clinical diagnosis. (Funded by the Congressionally Directed Medical Research Program and the National Institutes of Health; ClinicalTrials.gov number, NCT00785304.) PMID:21631321

Brain abnormalities detected on magnetic resonance imaging of amphetamine users presenting to an emergency department: a pilot study.

PubMed

Fatovich, Daniel M; McCoubrie, David L; Song, Swithin J; Rosen, David M; Lawn, Nick D; Daly, Frank F

2010-09-06

To determine the prevalence of occult brain abnormalities in magnetic resonance imaging of active amphetamine users. Prospective convenience study in a tertiary hospital emergency department (ED). Patients presenting to the ED for an amphetamine-related reason were eligible for inclusion. We collected demographic data, drug use data, and performed a mini-mental state examination (MMSE). The proportion of patients with an abnormality on their MRI scan. Of 38 patients enrolled, 30 had MRI scans. Nineteen were male and their mean age was 26.7 +/- 5.4 years (range 19-41 years). The mean age of first amphetamine use was 18 years (range 13-26 years). Sixteen patients used crystal methamphetamine (mean amount 2.5 g/week), nine used amphetamine ("speed") (mean amount 2.9 g/week), and 23 used ecstasy (mean amount 2.3 tablets/week). Marijuana was smoked by 26 (mean amount 5.9 g/week), and 28 drank alcohol (mean amount 207 g/week). The median MMSE score was 27/30 (interquartile range, 26-29). Abnormalities on brain MRI scans were identified in six patients, most commonly an unidentified bright object (n = 4). In this pilot study of brain MRI of young people attending the ED with an amphetamine-related presentation, one in five had an occult brain lesion. While the significance of this is uncertain, it is congruent with evidence that amphetamines cause brain injury.

Structural and Perfusion Abnormalities of Brain on MRI and Technetium-99m-ECD SPECT in Children With Cerebral Palsy: A Comparative Study.

PubMed

Rana, Kamer Singh; Narwal, Varun; Chauhan, Lokesh; Singh, Giriraj; Sharma, Monica; Chauhan, Suneel

2016-04-01

Cerebral palsy has traditionally been associated with hypoxic ischemic brain damage. This study was undertaken to demonstrate structural and perfusion brain abnormalities. Fifty-six children diagnosed clinically as having cerebral palsy were studied between 1 to 14 years of age and were subjected to 3 Tesla magnetic resonance imaging (MRI). Brain and Technetium-99m-ECD brain single-photon emission computed tomography (SPECT) scan. Male to female ratio was 1.8:1 with a mean age of 4.16 ± 2.274 years. Spastic cerebral palsy was the most common type, observed in 91%. Birth asphyxia was the most common etiology (69.6%). White matter changes (73.2%) such as periventricular leukomalacia and corpus callosal thinning were the most common findings on MRI. On SPECT all cases except one revealed perfusion impairments in different regions of brain. MRI is more sensitive in detecting white matter changes, whereas SPECT is better in detecting cortical and subcortical gray matter abnormalities of perfusion. © The Author(s) 2015.

Structural Brain Abnormalities in Successfully Treated HIV Infection: Associations With Disease and Cerebrospinal Fluid Biomarkers.

PubMed

van Zoest, Rosan A; Underwood, Jonathan; De Francesco, Davide; Sabin, Caroline A; Cole, James H; Wit, Ferdinand W; Caan, Matthan W A; Kootstra, Neeltje A; Fuchs, Dietmar; Zetterberg, Henrik; Majoie, Charles B L M; Portegies, Peter; Winston, Alan; Sharp, David J; Gisslén, Magnus; Reiss, Peter

2017-12-27

Brain structural abnormalities have been reported in persons living with human immunodeficiency virus (HIV; PLWH) who are receiving suppressive combination antiretroviral therapy (cART), but their pathophysiology remains unclear. We investigated factors associated with brain tissue volumes and white matter microstructure (fractional anisotropy) in 134 PLWH receiving suppressive cART and 79 comparable HIV-negative controls, aged ≥45 years, from the Comorbidity in Relation to AIDS cohort, using multimodal neuroimaging and cerebrospinal fluid biomarkers. Compared with controls, PLWH had lower gray matter volumes (-13.7 mL; 95% confidence interval, -25.1 to -2.2) and fractional anisotropy (-0.0073; 95% confidence interval, -.012 to -.0024), with the largest differences observed in those with prior clinical AIDS. Hypertension and the soluble CD14 concentration in cerebrospinal fluid were associated with lower fractional anisotropy. These associations were independent of HIV serostatus (Pinteraction = .32 and Pinteraction = .59, respectively) and did not explain the greater abnormalities in brain structure in relation to HIV infection. The presence of lower gray matter volumes and more white matter microstructural abnormalities in well-treated PLWH partly reflect a combination of historical effects of AIDS, as well as the more general influence of systemic factors, such as hypertension and ongoing neuroinflammation. Additional mechanisms explaining the accentuation of brain structure abnormalities in treated HIV infection remain to be identified. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

Disrupted modular organization of resting-state cortical functional connectivity in U.S. military personnel following concussive ‘mild’ blast-related traumatic brain injury†

PubMed Central

Han, Kihwan; Mac Donald, Christine L.; Johnson, Ann M.; Barnes, Yolanda; Wierzechowski, Linda; Zonies, David; Oh, John; Flaherty, Stephen; Fang, Raymond; Raichle, Marcus E.; Brody, David L.

2013-01-01

Blast-related traumatic brain injury (TBI) has been one of the “signature injuries” of the wars in Iraq and Afghanistan. However, neuroimaging studies in concussive ‘mild’ blast-related TBI have been challenging due to the absence of abnormalities in computed tomography or conventional magnetic resonance imaging (MRI) and the heterogeneity of the blast-related injury mechanisms. The goal of this study was to address these challenges utilizing single-subject, module-based graph theoretic analysis of resting-state functional MRI (fMRI) data. We acquired 20 minutes of resting-state fMRI in 63 U.S. military personnel clinically diagnosed with concussive blast-related TBI and 21 U.S. military controls who had blast exposures but no diagnosis of TBI. All subjects underwent an initial scan within 90 days post-injury and 65 subjects underwent a follow-up scan 6 to 12 months later. A second independent cohort of 40 U.S. military personnel with concussive blast-related TBI patients served as a validation dataset. The second independent cohort underwent an initial scan within 30 days post-injury. 75% of scans were of good quality, with exclusions primarily due to excessive subject motion. Network analysis of the subset of these subjects in the first cohort with good quality scans revealed spatially localized reductions in participation coefficient, a measure of between-module connectivity, in the TBI patients relative to the controls at the time of the initial scan. These group differences were less prominent on the follow-up scans. The 15 brain areas with the most prominent reductions in participation coefficient were next used as regions of interest (ROIs) for single-subject analyses. In the first TBI cohort, more subjects than would be expected by chance (27/47 versus 2/47 expected, p < 0.0001) had 3 or more brain regions with abnormally low between-module connectivity relative to the controls on the initial scans. On the follow-up scans, more subjects than expected by chance (5/37, p = 0.044) but fewer subjects than on the initial scans had 3 or more brain regions with abnormally low between-module connectivity. Analysis of the second TBI cohort validation dataset with no free parameters provided a partial replication; again more subjects than expected by chance (8/31, p = 0.006) had 3 or more brain regions with abnormally low between-module connectivity on the initial scans, but the numbers were not significant (2/27, p = 0.276) on the follow-up scans. A single-subject, multivariate analysis by probabilistic principal component analysis of the between-module connectivity in the 15 identified ROIs, showed that 31/47 subjects in the first TBI cohort were found to be abnormal relative to the controls on the initial scans. In the second TBI cohort, 9/31 patients were found to be abnormal in identical multivariate analysis with no free parameters. Again, there were not substantial differences on the follow-up scans. Taken together, these results indicate that single-subject, module-based graph theoretic analysis of resting-state fMRI provides potentially useful information for concussive blast-related TBI if high quality scans can be obtained. The underlying biological mechanisms and consequences of disrupted between-module connectivity are unknown, thus further studies are required. PMID:23968735

Comparison of brain volume abnormalities between ADHD and conduct disorder in adolescence

PubMed Central

Stevens, Michael C.; Haney-Caron, Emily

2012-01-01

Background Previous studies of brain structure abnormalities in conduct disorder and attention-deficit/hyperactivity disorder (ADHD) samples have been limited owing to cross-comorbidity, preventing clear understanding of which structural brain abnormalities might be specific to or shared by each disorder. To our knowledge, this study was the first direct comparison of grey and white matter volumes in diagnostically “pure” (i.e., no comorbidities) conduct disorder and ADHD samples. Methods Groups of adolescents with noncormobid conduct disorder and with noncomorbid, combined-subtype ADHD were compared with age- and sex-matched controls using DARTEL voxel-based analysis of T1-weighted brain structure images. Analysis of variance with post hoc analyses compared whole brain grey and white matter volumes among the groups. Results We included 24 adolescents in each study group. There was an overall 13% reduction in grey matter volume in adolescents with conduct disorder, reflecting numerous frontal, temporal, parietal and subcortical deficits. The same grey matter regions typically were not abnormal in those with ADHD. Deficits in frontal lobe regions previously identified in studies of patients with ADHD either were not detected, or group differences from controls were not as strong as those between the conduct disorder and control groups. White matter volume measurements did not differentiate conduct disorder and ADHD. Limitations Our modest sample sizes prevented meaningful examination of individual features of ADHD or conduct disorder, such as aggression, callousness, or hyperactive versus inattentive symptom subtypes. Conclusion The evidence supports theories of frontotemporal abnormalities in adolescents with conduct disorder, but raises questions about the prominence of frontal lobe and striatal structural abnormalities in those with noncomorbid, combined-subtype ADHD. The latter point is clinically important, given the widely held belief that ADHD is associated with numerous frontal lobe structural deficits, a conclusion that is not strongly supported following direct comparison of diagnostically pure groups. The results are important for future etiological studies, particularly those seeking to identify how early expression of specific brain structure abnormalities could potentiate the risk for antisocial behaviour. PMID:22663946

Neonatal brain resting-state functional connectivity imaging modalities.

PubMed

Mohammadi-Nejad, Ali-Reza; Mahmoudzadeh, Mahdi; Hassanpour, Mahlegha S; Wallois, Fabrice; Muzik, Otto; Papadelis, Christos; Hansen, Anne; Soltanian-Zadeh, Hamid; Gelovani, Juri; Nasiriavanaki, Mohammadreza

2018-06-01

Infancy is the most critical period in human brain development. Studies demonstrate that subtle brain abnormalities during this state of life may greatly affect the developmental processes of the newborn infants. One of the rapidly developing methods for early characterization of abnormal brain development is functional connectivity of the brain at rest. While the majority of resting-state studies have been conducted using magnetic resonance imaging (MRI), there is clear evidence that resting-state functional connectivity (rs-FC) can also be evaluated using other imaging modalities. The aim of this review is to compare the advantages and limitations of different modalities used for the mapping of infants' brain functional connectivity at rest. In addition, we introduce photoacoustic tomography, a novel functional neuroimaging modality, as a complementary modality for functional mapping of infants' brain.

MicroRNA profiling reveals new aspects of HIV neurodegeneration: caspase-6 regulates astrocyte survival.

PubMed

Noorbakhsh, Farshid; Ramachandran, Rithwik; Barsby, Nicola; Ellestad, Kristofor K; LeBlanc, Andrea; Dickie, Peter; Baker, Glen; Hollenberg, Morley D; Cohen, Eric A; Power, Christopher

2010-06-01

MicroRNAs (miRNAs) are small noncoding RNA molecules, which are known to regulate gene expression in physiological and pathological conditions. miRNA profiling was performed using brain tissue from patients with HIV encephalitis (HIVE), a neuroinflammatory/degenerative disorder caused by HIV infection of the brain. Microarray analysis showed differential expression of multiple miRNAs in HIVE compared to control brains. Target prediction and gene ontology enrichment analysis disclosed targeting of several gene families/biological processes by differentially expressed miRNAs (DEMs), with cell death-related genes, including caspase-6, showing a bias toward down-regulated DEMs. Consistent with the miRNA data, HIVE brains exhibited higher levels of caspase-6 transcripts compared with control patients. Immunohistochemical analysis showed localization of the cleaved form of caspase-6 in astrocytes in HIVE brain sections. Exposure of cultured human primary astrocytes to HIV viral protein R (Vpr) induced p53 up-regulation, loss of mitochondrial membrane potential, and caspase-6 activation followed by cell injury. Transgenic mice, expressing Vpr in microglial cells, demonstrated astrocyte apoptosis in brain, which was associated with caspase-6 activation and neurobehavioral abnormalities. Overall, these data point to previously unrecognized alterations in miRNA profile in the brain during HIV infection, which contribute to cell death through dysregulation of cell death machinery.

Cortical folding in post-traumatic stress disorder after motor vehicle accidents: Regional differences in gyrification.

PubMed

Chu, Chun; Xie, Bing; Qiu, Mingguo; Liu, Kaijun; Tan, Liwen; Wu, Yi; Chen, Wei; Zhang, Shaoxiang

2017-04-01

Structural and functional magnetic resonance imaging (MRI) studies have revealed evidence of brain abnormalities in post-traumatic stress disorder (PTSD) patients. Cortical complexity and local gyrification index (lGI) reflect potential biological processes associated with normal or abnormal cognitive functioning. In the current study, lGI was used to explore cortical folding in PTSD patients involved in motor vehicle accidents (MVA). MRI brain scans were acquired from 18 PTSD patients who had suffered MVA at least 6 months previously and 18 healthy control subjects. All MRI images were obtained on a 3-T Siemens MRI machine and the cortical folding was analyzed using the workflow provided by software FreeSurfer. A general FreeSurfer's general linear model was used in the group analysis. In addition, correlation analysis was performed between the average of lGI extracted from the significantly different areas and the data for the clinical scale. The PTSD patients had significantly greater Clinician-Administered PTSD Scale scores than the control group. The patients showed significantly reduced lGI in the left lateral orbitofrontal cortex, consistent with findings of previous volumetric studies on PTSD. But there were no significant correlations in the left lateral orbitofrontal cortex between Clinician-Administered PTSD Scale scores and lGI. We suggest that abnormal gyrification in PTSD patients can be an important indicator of neurodevelopment deficits and may indeed be a biological marker for PTSD. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

VP-Nets : Efficient automatic localization of key brain structures in 3D fetal neurosonography.

PubMed

Huang, Ruobing; Xie, Weidi; Alison Noble, J

2018-04-23

Three-dimensional (3D) fetal neurosonography is used clinically to detect cerebral abnormalities and to assess growth in the developing brain. However, manual identification of key brain structures in 3D ultrasound images requires expertise to perform and even then is tedious. Inspired by how sonographers view and interact with volumes during real-time clinical scanning, we propose an efficient automatic method to simultaneously localize multiple brain structures in 3D fetal neurosonography. The proposed View-based Projection Networks (VP-Nets), uses three view-based Convolutional Neural Networks (CNNs), to simplify 3D localizations by directly predicting 2D projections of the key structures onto three anatomical views. While designed for efficient use of data and GPU memory, the proposed VP-Nets allows for full-resolution 3D prediction. We investigated parameters that influence the performance of VP-Nets, e.g. depth and number of feature channels. Moreover, we demonstrate that the model can pinpoint the structure in 3D space by visualizing the trained VP-Nets, despite only 2D supervision being provided for a single stream during training. For comparison, we implemented two other baseline solutions based on Random Forest and 3D U-Nets. In the reported experiments, VP-Nets consistently outperformed other methods on localization. To test the importance of loss function, two identical models are trained with binary corss-entropy and dice coefficient loss respectively. Our best VP-Net model achieved prediction center deviation: 1.8 ± 1.4 mm, size difference: 1.9 ± 1.5 mm, and 3D Intersection Over Union (IOU): 63.2 ± 14.7% when compared to the ground truth. To make the whole pipeline intervention free, we also implement a skull-stripping tool using 3D CNN, which achieves high segmentation accuracy. As a result, the proposed processing pipeline takes a raw ultrasound brain image as input, and output a skull-stripped image with five detected key brain structures. Copyright © 2018 Elsevier B.V. All rights reserved.

Morphometric brain abnormalities in boys with conduct disorder.

PubMed

Huebner, Thomas; Vloet, Timo D; Marx, Ivo; Konrad, Kerstin; Fink, Gereon R; Herpertz, Sabine C; Herpertz-Dahlmann, Beate

2008-05-01

Children with the early-onset type of conduct disorder (CD) are at high risk for developing an antisocial personality disorder. Although there have been several neuroimaging studies on morphometric differences in adults with antisocial personality disorder, little is known about structural brain aberrations in boys with CD. Magnetic resonance imaging and voxel-based morphometry were used to assess abnormalities in gray matter volumes in 23 boys ages 12 to 17 years with CD (17 comorbid for attention-deficit/hyperactivity disorder) in comparison with age- and IQ-matched controls. Compared with healthy controls, mean gray matter volume was 6% smaller in the clinical group. Compared with controls, reduced gray matter volumes were found in the left orbitofrontal region and bilaterally in the temporal lobes, including the amygdala and hippocampus on the left side in the CD group. Regression analyses in the clinical group indicated an inverse association of hyperactive/impulsive symptoms and widespread gray matter abnormalities in the frontoparietal and temporal cortices. By contrast, CD symptoms correlated primarily with gray matter reductions in limbic brain structures. The data suggest that boys with CD and comorbid attention-deficit/hyperactivity disorder show brain abnormalities in frontolimbic areas that resemble structural brain deficits, which are typically observed in adults with antisocial behavior.

Volumetric structural brain abnormalities in men with schizophrenia or antisocial personality disorder.

PubMed

Barkataki, Ian; Kumari, Veena; Das, Mrigendra; Taylor, Pamela; Sharma, Tonmoy

2006-05-15

Brain abnormalities are found in association with antisocial personality disorder and schizophrenia, the two mental disorders most implicated in violent behaviour. Structural magnetic resonance imaging was used to investigate the whole brain, cerebellum, temporal lobe, lateral ventricles, caudate nucleus, putamen, thalamus, hippocampus, amygdala and the prefrontal, pre-motor, sensorimotor, occipito-parietal regions in 13 men with antisocial personality disorder, 13 men with schizophrenia and a history of violence, 15 men with schizophrenia without violent history and 15 healthy non-violent men. Compared to controls, the antisocial personality disorder group displayed reductions in whole brain volume and temporal lobe as well as increases in putamen volume. Both schizophrenia groups regardless of violence history exhibited increased lateral ventricle volume, while the schizophrenia group with violent history showed further abnormalities including reduced whole brain and hippocampal volumes and increased putamen size. The findings suggest that individuals with antisocial personality disorder as well as those with schizophrenia and a history of violence have common neural abnormalities, but also show neuro-anatomical differences. The processes by which they came to apparently common ground may, however, differ. The finding of temporal lobe reductions prevalent among those with antisocial personality disorder and hippocampal reduction in the violent men with schizophrenia contributes support for the importance of this region in mediating violent behaviour.

Structural MRI biomarkers of shared pathogenesis in autism spectrum disorder and epilepsy.

PubMed

Blackmon, Karen

2015-06-01

Etiological factors that contribute to a high comorbidity between autism spectrum disorder (ASD) and epilepsy are the subject of much debate. Does epilepsy cause ASD or are there common underlying brain abnormalities that increase the risk of developing both disorders? This review summarizes evidence from quantitative MRI studies to suggest that abnormalities of brain structure are not necessarily the consequence of ASD and epilepsy but are antecedent to disease expression. Abnormal gray and white matter volumes are present prior to onset of ASD and evident at the time of onset in pediatric epilepsy. Aberrant brain growth trajectories are also common in both disorders, as evidenced by blunted gray matter maturation and white matter maturation. Although the etiological factors that explain these abnormalities are unclear, high heritability estimates for gray matter volume and white matter microstructure demonstrate that genetic factors assert a strong influence on brain structure. In addition, histopathological studies of ASD and epilepsy brain tissue reveal elevated rates of malformations of cortical development (MCDs), such as focal cortical dysplasia and heterotopias, which supports disruption of neuronal migration as a contributing factor. Although MCDs are not always visible on MRI with conventional radiological analysis, quantitative MRI detection methods show high sensitivity to subtle malformations in epilepsy and can be potentially applied to MCD detection in ASD. Such an approach is critical for establishing quantitative neuroanatomic endophenotypes that can be used in genetic research. In the context of emerging drug treatments for seizures and autism symptoms, such as rapamycin and rapalogs, in vivo neuroimaging markers of subtle structural brain abnormalities could improve sample stratification in human clinical trials and potentially extend the range of patients that might benefit from treatment. This article is part of a Special Issue entitled "Autism and Epilepsy". Copyright © 2015 Elsevier Inc. All rights reserved.

Postural abnormalities and contraversive pushing following right hemisphere brain damage.

PubMed

Lafosse, C; Kerckhofs, E; Vereeck, L; Troch, M; Van Hoydonck, G; Moeremans, M; Sneyers, C; Broeckx, J; Dereymaeker, L

2007-06-01

We investigated the presence of postural abnormalities in a consecutive sample of stroke patients, with either left or right brain damage, in relation to their perceived body position in space. The presence or absence of posture-related symptoms was judged by two trained therapists and subsequently analysed by hierarchical classes analysis (HICLAS). The subject classes resulting from the HICLAS model were further validated with respect to posture-related measurements, such as centre of gravity position and head position, as well as measurements related to the postural body scheme, such as the perception of postural and visual verticality. The results of the classification analysis clearly demonstrated a relation between the presence of right brain damage and abnormalities in body geometry. The HICLAS model revealed three classes of subjects: The first class contained almost all the patients without neglect and without any signs of contraversive pushing. They were mainly characterised by a normal body axis in any position. The second class were all neglect patients but predominantly without any contraversive pushing. The third class contained right brain damaged patients, all showing neglect and mostly exhibiting contraversive pushing. The patients in the third class showed a clear resistance to bringing the weight over to the ipsilesional side when the therapist attempted to make the subject achieve a vertical posture across the midline. The clear correspondence between abnormalities of the observed body geometry and the tilt of the subjective postural and visual vertical suggests that a patient's postural body geometry is characterised by leaning towards the side of space where he/she feels aligned with an altered postural body scheme. The presence of contraversive pushing after right brain damage points in to a spatial higher-order processing deficit underlying the higher frequency and severity of the axial postural abnormalities found after right brain lesions.

Autism, the superior temporal sulcus and social perception.

PubMed

Zilbovicius, Monica; Meresse, Isabelle; Chabane, Nadia; Brunelle, Francis; Samson, Yves; Boddaert, Nathalie

2006-07-01

The most common clinical sign of autism spectrum disorders (ASD) is social interaction impairment, which is associated with communication deficits and stereotyped behaviors. Based on recent brain-imaging results, our hypothesis is that abnormalities in the superior temporal sulcus (STS) are highly implicated in ASD. STS abnormalities are characterized by decreased gray matter concentration, rest hypoperfusion and abnormal activation during social tasks. STS anatomical and functional anomalies occurring during early brain development could constitute the first step in the cascade of neural dysfunction underlying ASD. We will focus this review on the STS, which has been highly implicated in social cognition. We will review recent data on the contribution of the STS to normal social cognition and review brain-imaging data implicating this area in ASD. This review is part of the INMED/TINS special issue "Nature and nurture in brain development and neurological disorders", based on presentations at the annual INMED/TINS symposium (http://inmednet.com/).

Dysfunctional tubular endoplasmic reticulum constitutes a pathological feature of Alzheimer's disease.

PubMed

Sharoar, M G; Shi, Q; Ge, Y; He, W; Hu, X; Perry, G; Zhu, X; Yan, R

2016-09-01

Pathological features in Alzheimer's brains include mitochondrial dysfunction and dystrophic neurites (DNs) in areas surrounding amyloid plaques. Using a mouse model that overexpresses reticulon 3 (RTN3) and spontaneously develops age-dependent hippocampal DNs, here we report that DNs contain both RTN3 and REEPs, topologically similar proteins that can shape tubular endoplasmic reticulum (ER). Importantly, ultrastructural examinations of such DNs revealed gradual accumulation of tubular ER in axonal termini, and such abnormal tubular ER inclusion is found in areas surrounding amyloid plaques in biopsy samples from Alzheimer's disease (AD) brains. Functionally, abnormally clustered tubular ER induces enhanced mitochondrial fission in the early stages of DN formation and eventual mitochondrial degeneration at later stages. Furthermore, such DNs are abrogated when RTN3 is ablated in aging and AD mouse models. Hence, abnormally clustered tubular ER can be pathogenic in brain regions: disrupting mitochondrial integrity, inducing DNs formation and impairing cognitive function in AD and aging brains.

Functional brain MRI in patients complaining of electrohypersensitivity after long term exposure to electromagnetic fields.

PubMed

Heuser, Gunnar; Heuser, Sylvia A

2017-09-26

Ten adult patients with electromagnetic hypersensitivity underwent functional magnetic resonance imaging (fMRI) brain scans. All scans were abnormal with abnormalities which were consistent and similar. It is proposed that fMRI brain scans be used as a diagnostic aid for determining whether or not a patient has electromagnetic hypersensitivity. Over the years we have seen an increasing number of patients who had developed multi system complaints after long term repeated exposure to electromagnetic fields (EMFs). These complaints included headaches, intermittent cognitive and memory problems, intermittent disorientation, and also sensitivity to EMF exposure. Regular laboratory tests were within normal limits in these patients. The patients refused to be exposed to radioactivity. This of course ruled out positron emission tomography (PET) and single-photon emission computed tomography (SPECT) brain scanning. This is why we ordered fMRI brain scans on these patients. We hoped that we could document objective abnormalities in these patients who had often been labeled as psychiatric cases. Ten patients first underwent a regular magnetic resonance imaging (MRI) brain scan, using a 3 Tesla Siemens Verio MRI open system. A functional MRI study was then performed in the resting state using the following sequences: A three-dimensional, T1-weighted, gradient-echo (MPRAGE) Resting state network. The echo-planar imaging (EPI) sequences for this resting state blood oxygenation level dependent (BOLD) scan were then post processed on a 3D workstation and the independent component analysis was performed separating out the various networks. Arterial spin labeling. Tractography and fractional anisotropy. All ten patients had abnormal functional MRI brain scans. The abnormality was often described as hyper connectivity of the anterior component of the default mode in the medial orbitofrontal area. Other abnormalities were usually found. Regular MRI studies of the brain were mostly unremarkable in these patients. We propose that functional MRI studies should become a diagnostic aid when evaluating a patient who claims electrohypersensitivity (EHS) and has otherwise normal studies. Interestingly, the differential diagnosis for the abnormalities seen on the fMRI includes head injury. It turns out that many of our patients indeed had a history of head injury which was then followed sometime later by the development of EHS. Many of our patients also had a history of exposure to potentially neurotoxic chemicals, especially mold. Head injury and neurotoxic chemical exposure may make a patient more vulnerable to develop EHS.

Electroretinography and Visual Evoked Potentials in Childhood Brain Tumor Survivors.

PubMed

Pietilä, Sari; Lenko, Hanna L; Oja, Sakari; Koivisto, Anna-Maija; Pietilä, Timo; Mäkipernaa, Anne

2016-07-01

This population-based cross-sectional study evaluates the clinical value of electroretinography and visual evoked potentials in childhood brain tumor survivors. A flash electroretinography and a checkerboard reversal pattern visual evoked potential (or alternatively a flash visual evoked potential) were done for 51 survivors (age 3.8-28.7 years) after a mean follow-up time of 7.6 (1.5-15.1) years. Abnormal electroretinography was obtained in 1 case, bilaterally delayed abnormal visual evoked potentials in 22/51 (43%) cases. Nine of 25 patients with infratentorial tumor location, and altogether 12 out of 31 (39%) patients who did not have tumors involving the visual pathways, had abnormal visual evoked potentials. Abnormal electroretinographies are rarely observed, but abnormal visual evoked potentials are common even without evident anatomic lesions in the visual pathway. Bilateral changes suggest a general and possibly multifactorial toxic/adverse effect on the visual pathway. Electroretinography and visual evoked potential may have clinical and scientific value while evaluating long-term effects of childhood brain tumors and tumor treatment. © The Author(s) 2016.

Functional and clinical neuroanatomy of morality.

PubMed

Fumagalli, Manuela; Priori, Alberto

2012-07-01

Morality is among the most sophisticated features of human judgement, behaviour and, ultimately, mind. An individual who behaves immorally may violate ethical rules and civil rights, and may threaten others' individual liberty, sometimes becoming violent and aggressive. In recent years, neuroscience has shown a growing interest in human morality, and has advanced our understanding of the cognitive and emotional processes involved in moral decisions, their anatomical substrates and the neurology of abnormal moral behaviour. In this article, we review research findings that have provided a key insight into the functional and clinical neuroanatomy of the brain areas involved in normal and abnormal moral behaviour. The 'moral brain' consists of a large functional network including both cortical and subcortical anatomical structures. Because morality is a complex process, some of these brain structures share their neural circuits with those controlling other behavioural processes, such as emotions and theory of mind. Among the anatomical structures implicated in morality are the frontal, temporal and cingulate cortices. The prefrontal cortex regulates activity in subcortical emotional centres, planning and supervising moral decisions, and when its functionality is altered may lead to impulsive aggression. The temporal lobe is involved in theory of mind and its dysfunction is often implicated in violent psychopathy. The cingulate cortex mediates the conflict between the emotional and the rational components of moral reasoning. Other important structures contributing to moral behaviour include the subcortical nuclei such as the amygdala, hippocampus and basal ganglia. Brain areas participating in moral processing can be influenced also by genetic, endocrine and environmental factors. Hormones can modulate moral behaviour through their effects on the brain. Finally, genetic polymorphisms can predispose to aggressivity and violence, arguing for a genetic-based predisposition to morality. Because abnormal moral behaviour can arise from both functional and structural brain abnormalities that should be diagnosed and treated, the neurology of moral behaviour has potential implications for clinical practice and raises ethical concerns. Last, since research has developed several neuromodulation techniques to improve brain dysfunction (deep brain stimulation, transcranial magnetic stimulation and transcranial direct current stimulation), knowing more about the 'moral brain' might help to develop novel therapeutic strategies for neurologically based abnormal moral behaviour.

Abnormalities in Human Brain Creatine Metabolism in Gulf War Illness Probed with MRS

DTIC Science & Technology

2014-12-01

TYPE Final 3. DATES COVERED 30 Sep 2012 - 29 Sep 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Abnormalities in Human Brain Creatine Metabolism in...levels of total creatine (tCr) in veterans with Gulf War Illness have been observed in prior studies. The goal of this research is to estimate amounts and

Cross-Sectional and Longitudinal Abnormalities in Brain Structure in Children with Severe Mood Dysregulation or Bipolar Disorder

ERIC Educational Resources Information Center

Adleman, Nancy E.; Fromm, Stephen J.; Razdan, Varun; Kayser, Reilly; Dickstein, Daniel P.; Brotman, Melissa A.; Pine, Daniel S.; Leibenluft, Ellen

2012-01-01

Background: There is debate as to whether chronic irritability (operationalized as severe mood dysregulation, SMD) is a developmental form of bipolar disorder (BD). Although structural brain abnormalities in BD have been demonstrated, no study compares neuroanatomy among SMD, BD, and healthy volunteers (HV) either cross-sectionally or over time.…

Treatment-responsive limbic encephalitis identified by neuropil antibodies: MRI and PET correlates

PubMed Central

Ances, Beau M.; Vitaliani, Roberta; Taylor, Robert A.; Liebeskind, David S.; Voloschin, Alfredo; Houghton, David J.; Galetta, Steven L.; Dichter, Marc; Alavi, Abass; Rosenfeld, Myrna R.; Dalmau, Josep

2007-01-01

We report seven patients, six from a single institution, who developed subacute limbic encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [18F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50% of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal teratoma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigens concentrated in areas of high dendritic density or synaptic-enriched regions of the hippocampus or cerebellum. Preliminary characterization of these antigens indicates that they are diverse and expressed on the neuronal cell membrane and dendrites; they do not co-localize with VGKCs, but partially co-localize with spinophilin. A target autoantigen in one of the patients co-localizes with a cell surface protein involved in hippocampal dendritic development. All patients except the one with antibodies to intracellular antigens had dramatic clinical and neuroimaging responses to immunotherapy or tumour resection; two patients had neurological relapse and improved with immunotherapy. Overall, the phenotype associated with the novel neuropil antibodies includes dominant behavioural and psychiatric symptoms and seizures that often interfere with the evaluation of cognition and memory, and brain MRI or FDG-PET abnormalities less frequently restricted to the medial temporal lobes than in patients with classical paraneoplastic or VGKC antibodies. When compared with patients with VGKC antibodies, patients with these novel antibodies are more likely to have CSF inflammatory abnormalities and systemic tumours (teratoma and thymoma), and they do not develop SIADH-like hyponatraemia. Although most autoantigens await characterization, all share intense expression by the neuropil of hippocampus, with patterns of immunolabelling characteristic enough to suggest the diagnosis of these disorders and predict response to treatment. PMID:15888538

Resting state electrical brain activity and connectivity in fibromyalgia

PubMed Central

Vanneste, Sven; Ost, Jan; Van Havenbergh, Tony; De Ridder, Dirk

2017-01-01

The exact mechanism underlying fibromyalgia is unknown, but increased facilitatory modulation and/or dysfunctional descending inhibitory pathway activity are posited as possible mechanisms contributing to sensitization of the central nervous system. The primary goal of this study is to identify a fibromyalgia neural circuit that can account for these abnormalities in central pain. The second goal is to gain a better understanding of the functional connectivity between the default and the executive attention network (salience network plus dorsal lateral prefrontal cortex) in fibromyalgia. We examine neural activity associated with fibromyalgia (N = 44) and compare these with healthy controls (N = 44) using resting state source localized EEG. Our data support an important role of the pregenual anterior cingulate cortex but also suggest that the degree of activation and the degree of integration between different brain areas is important. The inhibition of the connectivity between the dorsal lateral prefrontal cortex and the posterior cingulate cortex on the pain inhibitory pathway seems to be limited by decreased functional connectivity with the pregenual anterior cingulate cortex. Our data highlight the functional dynamics of brain regions integrated in brain networks in fibromyalgia patients. PMID:28650974

Brain regions with abnormal network properties in severe epilepsy of Lennox-Gastaut phenotype: Multivariate analysis of task-free fMRI.

PubMed

Pedersen, Mangor; Curwood, Evan K; Archer, John S; Abbott, David F; Jackson, Graeme D

2015-11-01

Lennox-Gastaut syndrome, and the similar but less tightly defined Lennox-Gastaut phenotype, describe patients with severe epilepsy, generalized epileptic discharges, and variable intellectual disability. Our previous functional neuroimaging studies suggest that abnormal diffuse association network activity underlies the epileptic discharges of this clinical phenotype. Herein we use a data-driven multivariate approach to determine the spatial changes in local and global networks of patients with severe epilepsy of the Lennox-Gastaut phenotype. We studied 9 adult patients and 14 controls. In 20 min of task-free blood oxygen level-dependent functional magnetic resonance imaging data, two metrics of functional connectivity were studied: Regional homogeneity or local connectivity, a measure of concordance between each voxel to a focal cluster of adjacent voxels; and eigenvector centrality, a global connectivity estimate designed to detect important neural hubs. Multivariate pattern analysis of these data in a machine-learning framework was used to identify spatial features that classified disease subjects. Multivariate pattern analysis was 95.7% accurate in classifying subjects for both local and global connectivity measures (22/23 subjects correctly classified). Maximal discriminating features were the following: increased local connectivity in frontoinsular and intraparietal areas; increased global connectivity in posterior association areas; decreased local connectivity in sensory (visual and auditory) and medial frontal cortices; and decreased global connectivity in the cingulate cortex, striatum, hippocampus, and pons. Using a data-driven analysis method in task-free functional magnetic resonance imaging, we show increased connectivity in critical areas of association cortex and decreased connectivity in primary cortex. This supports previous findings of a critical role for these association cortical regions as a final common pathway in generating the Lennox-Gastaut phenotype. Abnormal function of these areas is likely to be important in explaining the intellectual problems characteristic of this disorder. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Regional homogeneity of resting-state brain abnormalities in bipolar and unipolar depression.

PubMed

Liu, Chun-Hong; Ma, Xin; Wu, Xia; Zhang, Yu; Zhou, Fu-Chun; Li, Feng; Tie, Chang-Le; Dong, Jie; Wang, Yong-Jun; Yang, Zhi; Wang, Chuan-Yue

2013-03-05

Bipolar disorder patients experiencing a depressive episode (BD-dep) without an observed history of mania are often misdiagnosed and are consequently treated as having unipolar depression (UD), leading to inadequate treatment and poor outcomes. An essential solution to this problem is to identify objective biological markers that distinguish BD-dep and UD patients at an early stage. However, studies directly comparing the brain dysfunctions associated with BD-dep and UD are rare. More importantly, the specificity of the differences in brain activity between these mental disorders has not been examined. With whole-brain regional homogeneity analysis and region-of-interest (ROI) based receiver operating characteristic (ROC) analysis, we aimed to compare the resting-state brain activity of BD-dep and UD patients. Furthermore, we examined the specific differences and whether these differences were attributed to the brain abnormality caused by BD-dep, UD, or both. Twenty-one bipolar and 21 unipolar depressed patients, as well as 26 healthy subjects matched for gender, age, and educational levels, participated in the study. We compared the differences in the regional homogeneity (ReHo) of the BD-dep and UD groups and further identified their pathophysiological abnormality. In the brain regions showing a difference between the BD-dep and UD groups, we further conducted receptive operation characteristic (ROC) analyses to confirm the effectiveness of the identified difference in classifying the patients. We observed ReHo differences between the BD-dep and UD groups in the right ventrolateral middle frontal gyrus, right dorsal anterior insular, right ventral anterior insular, right cerebellum posterior gyrus, right posterior cingulate cortex, right parahippocampal gyrus, and left cerebellum anterior gyrus. Further ROI comparisons and ROC analysis on these ROIs showed that the right parahippocampal gyrus reflected abnormality specific to the BD-dep group, while the right middle frontal gyrus, the right dorsal anterior insular, the right cerebellum posterior gyrus, and the right posterior cingulate cortex showed abnormality specific to the UD group. We found brain regions showing resting state ReHo differences and examined their sensitivity and specificity, suggesting a potential neuroimaging biomarker to distinguish between BD-dep and UD patients. We further clarified the pathophysiological abnormality of these regions for each of the two patient populations. Copyright © 2012 Elsevier Inc. All rights reserved.

Epilepsy in the setting of full trisomy 18: A multicenter study on 18 affected children with and without structural brain abnormalities.

PubMed

Matricardi, Sara; Spalice, Alberto; Salpietro, Vincenzo; Di Rosa, Gabriella; Balistreri, Maria Cristina; Grosso, Salvatore; Parisi, Pasquale; Elia, Maurizio; Striano, Pasquale; Accorsi, Patrizia; Cusmai, Raffaella; Specchio, Nicola; Coppola, Giangennaro; Savasta, Salvatore; Carotenuto, Marco; Tozzi, Elisabetta; Ferrara, Pietro; Ruggieri, Martino; Verrotti, Alberto

2016-09-01

This paper reports on the clinical aspects, electroencephalographic (EEG) features, and neuroimaging findings in children with full trisomy 18 and associated epilepsy, and compares the evolution and outcome of their neurological phenotype. We retrospectively studied 18 patients (10 males and 8 females; aged 14 months to 9 years) with full trisomy 18 and epilepsy. All patients underwent comprehensive assessment including neuroimaging studies of the brain. We divided patients into two groups according to neuroimaging findings: (Group 1) 10 patients harboring structural brain malformations, and (Group 2) 8 patients with normal brain images. Group 1 had a significantly earlier age at seizure onset (2 months) compared to Group 2 (21 months). The seizure semiology was more severe in Group 1, who presented multiple seizure types, need for polytherapy (80% of patients), multifocal EEG abnormalities and poorer outcome (drug resistant epilepsy in 90% of patients) than Group 2 who presented a single seizure type, generalized or focal, and non-specific EEG pattern; these patients were successfully treated with monotherapy with good outcome. Imaging revealed a wide and complex spectrum of structural brain abnormalities including anomalies of the commissures, cerebellar malformations, cortical abnormalities, and various degrees of cortical atrophy. Epilepsy in full trisomy 18 may develop during the first months of life and can be associated with structural brain malformations. Patients with brain malformations can show multiple seizure types and can frequently be resistant to therapy with antiepileptic drugs. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

An anatomically comprehensive atlas of the adult human brain transcriptome

PubMed Central

Guillozet-Bongaarts, Angela L.; Shen, Elaine H.; Ng, Lydia; Miller, Jeremy A.; van de Lagemaat, Louie N.; Smith, Kimberly A.; Ebbert, Amanda; Riley, Zackery L.; Abajian, Chris; Beckmann, Christian F.; Bernard, Amy; Bertagnolli, Darren; Boe, Andrew F.; Cartagena, Preston M.; Chakravarty, M. Mallar; Chapin, Mike; Chong, Jimmy; Dalley, Rachel A.; David Daly, Barry; Dang, Chinh; Datta, Suvro; Dee, Nick; Dolbeare, Tim A.; Faber, Vance; Feng, David; Fowler, David R.; Goldy, Jeff; Gregor, Benjamin W.; Haradon, Zeb; Haynor, David R.; Hohmann, John G.; Horvath, Steve; Howard, Robert E.; Jeromin, Andreas; Jochim, Jayson M.; Kinnunen, Marty; Lau, Christopher; Lazarz, Evan T.; Lee, Changkyu; Lemon, Tracy A.; Li, Ling; Li, Yang; Morris, John A.; Overly, Caroline C.; Parker, Patrick D.; Parry, Sheana E.; Reding, Melissa; Royall, Joshua J.; Schulkin, Jay; Sequeira, Pedro Adolfo; Slaughterbeck, Clifford R.; Smith, Simon C.; Sodt, Andy J.; Sunkin, Susan M.; Swanson, Beryl E.; Vawter, Marquis P.; Williams, Derric; Wohnoutka, Paul; Zielke, H. Ronald; Geschwind, Daniel H.; Hof, Patrick R.; Smith, Stephen M.; Koch, Christof; Grant, Seth G. N.; Jones, Allan R.

2014-01-01

Neuroanatomically precise, genome-wide maps of transcript distributions are critical resources to complement genomic sequence data and to correlate functional and genetic brain architecture. Here we describe the generation and analysis of a transcriptional atlas of the adult human brain, comprising extensive histological analysis and comprehensive microarray profiling of ~900 neuroanatomically precise subdivisions in two individuals. Transcriptional regulation varies enormously by anatomical location, with different regions and their constituent cell types displaying robust molecular signatures that are highly conserved between individuals. Analysis of differential gene expression and gene co-expression relationships demonstrates that brain-wide variation strongly reflects the distributions of major cell classes such as neurons, oligodendrocytes, astrocytes and microglia. Local neighbourhood relationships between fine anatomical subdivisions are associated with discrete neuronal subtypes and genes involved with synaptic transmission. The neocortex displays a relatively homogeneous transcriptional pattern, but with distinct features associated selectively with primary sensorimotor cortices and with enriched frontal lobe expression. Notably, the spatial topography of the neocortex is strongly reflected in its molecular topography— the closer two cortical regions, the more similar their transcriptomes. This freely accessible online data resource forms a high-resolution transcriptional baseline for neurogenetic studies of normal and abnormal human brain function. PMID:22996553

Brain Aneurysm

MedlinePlus

A brain aneurysm is an abnormal bulge or "ballooning" in the wall of an artery in the brain. They are sometimes called berry aneurysms because they ... often the size of a small berry. Most brain aneurysms produce no symptoms until they become large, ...

Surface-based brain morphometry and diffusion tensor imaging in schizoaffective disorder.

PubMed

Landin-Romero, Ramón; Canales-Rodríguez, Erick J; Kumfor, Fiona; Moreno-Alcázar, Ana; Madre, Mercè; Maristany, Teresa; Pomarol-Clotet, Edith; Amann, Benedikt L

2017-01-01

The profile of grey matter abnormalities and related white-matter pathology in schizoaffective disorder has only been studied to a limited extent. The aim of this study was to identify grey- and white-matter abnormalities in patients with schizoaffective disorder using complementary structural imaging techniques. Forty-five patients meeting Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition criteria and Research Diagnostic Criteria for schizoaffective disorder and 45 matched healthy controls underwent structural-T1 and diffusion magnetic resonance imaging to enable surface-based brain morphometry and diffusion tensor imaging analyses. Analyses were conducted to determine group differences in cortical volume, cortical thickness and surface area, as well as in fractional anisotropy and mean diffusivity. At a threshold of p = 0.05 corrected, all measures revealed significant differences between patients and controls at the group level. Spatial overlap of abnormalities was observed across the various structural neuroimaging measures. In grey matter, patients with schizoaffective disorder showed abnormalities in the frontal and temporal lobes, striatum, fusiform, cuneus, precuneus, lingual and limbic regions. White-matter abnormalities were identified in tracts connecting these areas, including the corpus callosum, superior and inferior longitudinal fasciculi, anterior thalamic radiation, uncinate fasciculus and cingulum bundle. The spatial overlap of abnormalities across the different imaging techniques suggests widespread and consistent brain pathology in schizoaffective disorder. The abnormalities were mainly detected in areas that have commonly been reported to be abnormal in schizophrenia, and to some extent in bipolar disorder, which may explain the clinical and aetiological overlap in these disorders.

Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities

PubMed Central

Janušonis, Skirmantas

2005-01-01

Background A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. Results The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. Conclusion At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies. PMID:16029508

Statistical distribution of blood serotonin as a predictor of early autistic brain abnormalities.

PubMed

Janusonis, Skirmantas

2005-07-19

A wide range of abnormalities has been reported in autistic brains, but these abnormalities may be the result of an earlier underlying developmental alteration that may no longer be evident by the time autism is diagnosed. The most consistent biological finding in autistic individuals has been their statistically elevated levels of 5-hydroxytryptamine (5-HT, serotonin) in blood platelets (platelet hyperserotonemia). The early developmental alteration of the autistic brain and the autistic platelet hyperserotonemia may be caused by the same biological factor expressed in the brain and outside the brain, respectively. Unlike the brain, blood platelets are short-lived and continue to be produced throughout the life span, suggesting that this factor may continue to operate outside the brain years after the brain is formed. The statistical distributions of the platelet 5-HT levels in normal and autistic groups have characteristic features and may contain information about the nature of this yet unidentified factor. The identity of this factor was studied by using a novel, quantitative approach that was applied to published distributions of the platelet 5-HT levels in normal and autistic groups. It was shown that the published data are consistent with the hypothesis that a factor that interferes with brain development in autism may also regulate the release of 5-HT from gut enterochromaffin cells. Numerical analysis revealed that this factor may be non-functional in autistic individuals. At least some biological factors, the abnormal function of which leads to the development of the autistic brain, may regulate the release of 5-HT from the gut years after birth. If the present model is correct, it will allow future efforts to be focused on a limited number of gene candidates, some of which have not been suspected to be involved in autism (such as the 5-HT4 receptor gene) based on currently available clinical and experimental studies.

Magnetic resonance imaging in patients with obsessive-compulsive disorder with good versus poor insight.

PubMed

Aigner, Martin; Zitterl, Werner; Prayer, Daniela; Demal, Ulrike; Bach, Michael; Prayer, Lucas; Stompe, Thomas; Lenz, Gerhard

2005-11-30

The DSM-IV provides two subtypes of obsessive-compulsive disorder (OCD), labelled as OCD with insight and OCD with poor insight. For the latter, patients generally fail to recognize that the obsessions or compulsions are excessive or unreasonable. Several studies have shown significant brain abnormalities in OCD patients. However, at present, it remains unclear whether a specific pattern of structural brain abnormalities is related to poor insight in OCD. In the present study, magnetic resonance imaging (MRI) findings were compared in OCD patients with insight versus those with poor insight. Outpatients with diagnoses of OCD according to DSM-IV (300.30) and ICD-10 (F42) (n = 84; mean age 38+/-13; 35 females, 49 males) were dichotomized into the two subtypes. All subjects underwent an MRI examination. MRI findings were rated as "MRI abnormality" and "normal MRI." In our sample, 48% of the patients had MRI abnormalities. There was a highly significant difference between the two groups according to frequencies of MRI abnormalities, with 83% of the patients with poor insight showing MRI abnormalities compared with only 21% of the patients with insight. The specifier "poor insight" helps to identify a subgroup of OCD with a higher frequency of brain abnormalities of various types. This distinction should be taken into account in future studies concerning the course and therapeutic outcome of OCD.

TorsinA dysfunction causes persistent neuronal nuclear pore defects.

PubMed

Pappas, Samuel S; Liang, Chun-Chi; Kim, Sumin; Rivera, CheyAnne O; Dauer, William T

2018-02-01

A critical challenge to deciphering the pathophysiology of neurodevelopmental disease is identifying which of the myriad abnormalities that emerge during CNS maturation persist to contribute to long-term brain dysfunction. Childhood-onset dystonia caused by a loss-of-function mutation in the AAA+ protein torsinA exemplifies this challenge. Neurons lacking torsinA develop transient nuclear envelope (NE) malformations during CNS maturation, but no NE defects are described in mature torsinA null neurons. We find that during postnatal CNS maturation torsinA null neurons develop mislocalized and dysfunctional nuclear pore complexes (NPC) that lack NUP358, normally added late in NPC biogenesis. SUN1, a torsinA-related molecule implicated in interphase NPC biogenesis, also exhibits localization abnormalities. Whereas SUN1 and associated nuclear membrane abnormalities resolve in juvenile mice, NPC defects persist into adulthood. These findings support a role for torsinA function in NPC biogenesis during neuronal maturation and implicate altered NPC function in dystonia pathophysiology. © The Author(s) 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

Brain Growth Across the Life Span in Autism: Age-Specific Changes in Anatomical Pathology

PubMed Central

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2014-01-01

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has lead to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism there may also be age-specific changes in gene expression, molecular, synaptic, cellular and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. PMID:20920490

Comprehensive Behavioral Analysis of Activating Transcription Factor 5-Deficient Mice

PubMed Central

Umemura, Mariko; Ogura, Tae; Matsuzaki, Ayako; Nakano, Haruo; Takao, Keizo; Miyakawa, Tsuyoshi; Takahashi, Yuji

2017-01-01

Activating transcription factor 5 (ATF5) is a member of the CREB/ATF family of basic leucine zipper transcription factors. We previously reported that ATF5-deficient (ATF5-/-) mice demonstrated abnormal olfactory bulb development due to impaired interneuron supply. Furthermore, ATF5-/- mice were less aggressive than ATF5+/+ mice. Although ATF5 is widely expressed in the brain, and involved in the regulation of proliferation and development of neurons, the physiological role of ATF5 in the higher brain remains unknown. Our objective was to investigate the physiological role of ATF5 in the higher brain. We performed a comprehensive behavioral analysis using ATF5-/- mice and wild type littermates. ATF5-/- mice exhibited abnormal locomotor activity in the open field test. They also exhibited abnormal anxiety-like behavior in the light/dark transition test and open field test. Furthermore, ATF5-/- mice displayed reduced social interaction in the Crawley’s social interaction test and increased pain sensitivity in the hot plate test compared with wild type. Finally, behavioral flexibility was reduced in the T-maze test in ATF5-/- mice compared with wild type. In addition, we demonstrated that ATF5-/- mice display disturbances of monoamine neurotransmitter levels in several brain regions. These results indicate that ATF5 deficiency elicits abnormal behaviors and the disturbance of monoamine neurotransmitter levels in the brain. The behavioral abnormalities of ATF5-/- mice may be due to the disturbance of monoamine levels. Taken together, these findings suggest that ATF5-/- mice may be a unique animal model of some psychiatric disorders. PMID:28744205

Degree connectivity in body dysmorphic disorder and relationships with obsessive and compulsive symptoms.

PubMed

Beucke, Jan C; Sepulcre, Jorge; Buhlmann, Ulrike; Kathmann, Norbert; Moody, Teena; Feusner, Jamie D

2016-10-01

Individuals with body dysmorphic disorder (BDD) and obsessive-compulsive disorder (OCD) are categorized within the same major diagnostic group and both show regional brain hyperactivity in the orbitofrontal cortex (OFC) and the basal ganglia during symptom provocation. While recent studies revealed that degree connectivity of these areas is abnormally high in OCD and positively correlates with symptom severity, no study has investigated degree connectivity in BDD. We used functional magnetic resonance imaging (fMRI) to compare the local and distant degree of functional connectivity in all brain areas between 28 unmedicated BDD participants and 28 demographically matched healthy controls during a face-processing task. Correlational analyses tested for associations between degree connectivity and symptom severity assessed by the BDD version of the Yale-Brown obsessive-compulsive scale (BDD-Y-BOCS). Reduced local amygdalar connectivity was found in participants with BDD. No differences in distant connectivity were found. BDD-Y-BOCS scores significantly correlated with the local connectivity of the posterior-lateral OFC, and distant connectivity of the posterior-lateral and post-central OFC, respectively. These findings represent preliminary evidence that individuals with BDD exhibit brain-behavioral associations related to obsessive thoughts and compulsive behaviors that are highly similar to correlations previously found in OCD, further underscoring their related pathophysiology. This relationship could be further elucidated through investigation of resting-state functional connectivity in BDD, ideally in direct comparison with OCD and other obsessive-compulsive and related disorders. Copyright © 2016 Elsevier B.V. and ECNP. All rights reserved.

Neurologic Correlates of Gait Abnormalities in Cerebral Palsy: Implications for Treatment

PubMed Central

Zhou, Joanne; Butler, Erin E.; Rose, Jessica

2017-01-01

Cerebral palsy (CP) is the most common movement disorder in children. A diagnosis of CP is often made based on abnormal muscle tone or posture, a delay in reaching motor milestones, or the presence of gait abnormalities in young children. Neuroimaging of high-risk neonates and of children diagnosed with CP have identified patterns of neurologic injury associated with CP, however, the neural underpinnings of common gait abnormalities remain largely uncharacterized. Here, we review the nature of the brain injury in CP, as well as the neuromuscular deficits and subsequent gait abnormalities common among children with CP. We first discuss brain injury in terms of mechanism, pattern, and time of injury during the prenatal, perinatal, or postnatal period in preterm and term-born children. Second, we outline neuromuscular deficits of CP with a focus on spastic CP, characterized by muscle weakness, shortened muscle-tendon unit, spasticity, and impaired selective motor control, on both a microscopic and functional level. Third, we examine the influence of neuromuscular deficits on gait abnormalities in CP, while considering emerging information on neural correlates of gait abnormalities and the implications for strategic treatment. This review of the neural basis of gait abnormalities in CP discusses what is known about links between the location and extent of brain injury and the type and severity of CP, in relation to the associated neuromuscular deficits, and subsequent gait abnormalities. Targeted treatment opportunities are identified that may improve functional outcomes for children with CP. By providing this context on the neural basis of gait abnormalities in CP, we hope to highlight areas of further research that can reduce the long-term, debilitating effects of CP. PMID:28367118

Continuity of neuropil threads with tangle-bearing and tangle-free neurons in Alzheimer disease cortex. A confocal laser scanning microscopy study.

PubMed

Schmidt, M L; Murray, J M; Trojanowski, J Q

1993-04-01

Neuropil threads (NTs) are abnormal processes that are associated with tangle-bearing neurons in gray matter areas of Alzheimer disease (AD) brains. Although NTs contain paired helical filaments (PHFs) and share multiple tau epitopes with neurobrillary tangles (NFTs), the relationship between NTs and tangle-bearing neurons is unclear. For this reason, we assessed the continuity of NTs with tangle-bearing and tangle-free neurons. Since astrocytes express low levels of tau and rarely have been shown to contain PHFs, we also examined the relationship of NTs to cortical astrocytes. This was done using histochemical and immunochemical methods in conjunction with confocal laser scanning microscopy to examine NTs in amygdala and entorhinal cortex of seven AD brains. Only a small fraction of NTs (< 1%) in 3.5 x 10(6) microns 3 of amygdala and entorhinal cortex could be traced to local neurons with NFTs or to neurons that did not contain NFTs, and no NTs were continuous with cortical astrocytes. These results indicate that only a very small percentage of NTs in entorhinal cortex and amygdala occur in the most proximal segments of processes that emanate from tangle-bearing or tangle-free neurons. This implies that the majority of NTs reside in the distal parts of dendrites and/or the terminal arborizations of axons or that NTs are discontinuous abnormalities. Taken together, these data suggest that NTs could disrupt local and long distance neuronal circuitry and thereby contribute to the cognitive impairments seen in AD patients.

Reduced miR-512 and the Elevated Expression of Its Targets cFLIP and MCL1 Localize to Neurons With Hyperphosphorylated Tau Protein in Alzheimer Disease.

PubMed

Mezache, Louisa; Mikhail, Madison; Garofalo, Michela; Nuovo, Gerard J

2015-10-01

The cause for the neurofibrillary tangles and plaques in Alzheimer disease likely relates to an abnormal accumulation of their key components, which include β-amyloid and hyperphosphorylated tau protein. We segregated Alzheimer brain sections from people with end-stage disease into those with abundant hyperphosphorylated tau protein and those without and compared each to normal brains for global microRNA patterns. A significant reduced expression of several microRNAs, including miR-512, was evident in the Alzheimer brain sections with abundant hyperphosphorylated tau. Immunohistochemistry documented that 2 known targets of microRNA-512, cFLIP and MCL1, were significantly over expressed and each colocalized to neurons with the abnormal tau protein. Analysis for apoptosis including activated caspase-3, increased caspase-4 and caspase-8, apoptosis initiating factor, APAF-1 activity, and the TUNEL assay was negative in the areas where neurons showed hyperphosphorylated tau. MCM2 expression, a marker of neuroprogenitor cells, was significantly reduced in the Alzheimer sections that contained the hyperphosphorylated tau. These results suggest that a basic defect in Alzheimer disease may be the reduced microRNA-driven increased expression of proteins that may alter the apoptotic/antiapoptotic balance of neurons. This, in turn, could lead to the accumulation of key Alzheimer proteins such as hyperphosphorylated tau that ultimately prevent normal neuronal function and lead to disease symptomatology.

A Cross-Sectional and Follow-Up Functional MRI Study with a Working Memory Task in Adolescent Anorexia Nervosa

ERIC Educational Resources Information Center

Castro-Fornieles, Josefina; Caldu, Xavier; Andres-Perpina, Susana; Lazaro, Luisa; Bargallo, Nuria; Falcon, Carles; Plana, Maria Teresa; Junque, Carme

2010-01-01

Structural and functional brain abnormalities have been described in anorexia nervosa (AN). The objective of this study was to examine whether there is abnormal regional brain activation during a working memory task not associated with any emotional stimuli in adolescent patients with anorexia and to detect possible changes after weight recovery.…

Autism Spectrum Disorder as Early Neurodevelopmental Disorder: Evidence from the Brain Imaging Abnormalities in 2-3 Years Old Toddlers

ERIC Educational Resources Information Center

Xiao, Zhou; Qiu, Ting; Ke, Xiaoyan; Xiao, Xiang; Xiao, Ting; Liang, Fengjing; Zou, Bing; Huang, Haiqing; Fang, Hui; Chu, Kangkang; Zhang, Jiuping; Liu, Yijun

2014-01-01

Autism spectrum disorder (ASD) is a complex neurodevelopmental condition that occurs within the first 3 years of life, which is marked by social skills and communication deficits along with stereotyped repetitive behavior. Although great efforts have been made to clarify the underlying neuroanatomical abnormalities and brain-behavior relationships…

Increased Amplitude of Thalamocortical Low-Frequency Oscillations in Patients with Migraine

PubMed Central

Wilcox, Sophie L.; Veggeberg, Rosanna; Noseda, Rodrigo; Burstein, Rami; Borsook, David; Becerra, Lino

2016-01-01

For many years, neurobiological theories have emphasized the importance of neuronal oscillations in the emergence of brain function. At the same time, clinical studies have shown that disturbances or irregularities in brain rhythms may relate to various common neurological conditions, including migraine. Increasing evidence suggests that the CNS plays a fundamental role in the predisposition to develop different forms of headache. Here, we present human imaging data that strongly support the presence of abnormal low-frequency oscillations (LFOs) in thalamocortical networks of patients in the interictal phase of migraine. Our results show that the main source of arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus. In addition, spontaneous LFOs in the thalamus were selectively associated with the headache attack frequency, meaning that the varying amplitude of dysrhythmia could predispose patients to recurrent attacks. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability. We further speculate that the intrinsic dynamics of thalamocortical network oscillations are crucial for early sensory processing and therefore could underlie important pathophysiological processes involved in multisensory integration. SIGNIFICANCE STATEMENT In many cases, migraine attacks are thought to begin centrally. A major obstacle to studying intrinsic brain activity has been the identification of the precise anatomical structures and functional networks that are involved in migraine. Here, we present imaging data that strongly support the presence of abnormal low-frequency oscillations in thalamocortical networks of patients in the interictal phase of migraine. This arrhythmic activity was localized to the higher-order thalamic relays of the medial dorsal nucleus and was selectively associated with headache attack frequency. Rhythmic cortical feedback to the thalamus is a major factor in the amplification of thalamocortical oscillations, making it a strong candidate for influencing neuronal excitability and higher-level processes involved in multisensory integration. PMID:27466345

Childhood Brain Tumors

MedlinePlus

Brain tumors are abnormal growths inside the skull. They are among the most common types of childhood ... still be serious. Malignant tumors are cancerous. Childhood brain and spinal cord tumors can cause headaches and ...

Leukoencephalopathy with brain stem and spinal cord involvement and high lactate: a genetically proven case without elevated white matter lactate.

PubMed

Sharma, Suvasini; Sankhyan, Naveen; Kumar, Atin; Scheper, Gert C; van der Knaap, Marjo S; Gulati, Sheffali

2011-06-01

A 17-year-old Indian boy with gradually progressive ataxia with onset at 12 years of age is described. Magnetic resonance imaging (MRI) of the brain revealed extensive, inhomogeneous signal abnormalities in the cerebral white matter, with involvement of selected tracts in the brain stem and spinal cord. The imaging findings were characteristic of leukoencephalopathy with brain stem and spinal cord involvement and high lactate, a recently described leukodystrophy. Interestingly, magnetic resonance spectroscopy of the abnormal white matter did not reveal elevated lactate. The patient was compound heterozygous for 2 new mutations in DARS2, genetically confirming the diagnosis.

Computational Approach to Schizophrenia: Disconnection Syndrome and Dynamical Pharmacology

NASA Astrophysics Data System (ADS)

Érdi, Péter; Flaugher, Brad; Jones, Trevor; Ujfalussy, Balázs; Zalányi, László; Diwadkar, Vaibhav A.

2008-07-01

Schizophrenia may be best understood in terms of abnormal interactions between different brain regions. Tasks such as associative learning that engage different brain regions may be ideal for studying altered brain function in the illness. Preliminary data suggest that the hippocampus is involved in the encoding (learning) and the prefrontal cortex in the retrieval of associative memories. Specific changes in the fMRI activities have also been observed based on comparative studies between stable schizophrenia patients and healthy control subjects. Disconnectivity, observed between brain regions in schizophrenic patients could result from abnormal modulation of N-methyl-D-aspartate (NMDA)-dependent plasticity implicated in schizophrenia.

A mechanical model predicts morphological abnormalities in the developing human brain

NASA Astrophysics Data System (ADS)

Budday, Silvia; Raybaud, Charles; Kuhl, Ellen

2014-07-01

The developing human brain remains one of the few unsolved mysteries of science. Advancements in developmental biology, neuroscience, and medical imaging have brought us closer than ever to understand brain development in health and disease. However, the precise role of mechanics throughout this process remains underestimated and poorly understood. Here we show that mechanical stretch plays a crucial role in brain development. Using the nonlinear field theories of mechanics supplemented by the theory of finite growth, we model the human brain as a living system with a morphogenetically growing outer surface and a stretch-driven growing inner core. This approach seamlessly integrates the two popular but competing hypotheses for cortical folding: axonal tension and differential growth. We calibrate our model using magnetic resonance images from very preterm neonates. Our model predicts that deviations in cortical growth and thickness induce morphological abnormalities. Using the gyrification index, the ratio between the total and exposed surface area, we demonstrate that these abnormalities agree with the classical pathologies of lissencephaly and polymicrogyria. Understanding the mechanisms of cortical folding in the developing human brain has direct implications in the diagnostics and treatment of neurological disorders, including epilepsy, schizophrenia, and autism.

Cognitive correlates of gray matter abnormalities in adolescent siblings of patients with childhood-onset schizophrenia

PubMed Central

Wagshal, Dana; Knowlton, Barbara Jean; Cohen, Jessica Rachel; Bookheimer, Susan Yost; Bilder, Robert Martin; Fernandez, Vindia Gisela; Asarnow, Robert Franklin

2015-01-01

Patients with childhood onset schizophrenia (COS) display widespread gray matter (GM) structural brain abnormalities. Healthy siblings of COS patients share some of these structural abnormalities, suggesting that GM abnormalities are endophenotypes for schizophrenia. Another possible endophenotype for schizophrenia that has been relatively unexplored is corticostriatal dysfunction. The corticostriatal system plays an important role in skill learning. Our previous studies have demonstrated corticostriatal dysfunction in COS siblings with a profound skill learning deficit and abnormal pattern of brain activation during skill learning. This study investigated whether structural abnormalities measured using volumetric brain morphometry (VBM) were present in siblings of COS patients and whether these were related to deficits in cognitive skill learning. Results revealed smaller GM volume in COS siblings relative to controls in a number of regions, including occipital, parietal, and subcortical regions including the striatum, and greater GM volume relative to controls in several subcortical regions. Volume in the right superior frontal gyrus and cerebellum were related to performance differences between groups on the weather prediction task, a measure of cognitive skill learning. Our results support the idea that corticostriatal and cerebellar impairment in unaffected siblings of COS patients are behaviorally relevant and may reflect genetic risk for schizophrenia. PMID:25541139

Interictal Electroencephalography (EEG) Findings in Children with Epilepsy and Bilateral Brain Lesions on Magnetic Resonance Imaging (MRI).

PubMed

Zubcevic, Smail; Milos, Maja; Catibusic, Feriha; Uzicanin, Sajra; Krdzalic, Belma

2015-12-01

Neuroimaging procedures and electroencephalography (EEG) are basic parts of investigation of patients with epilepsies. The aim is to try to assess relationship between bilaterally localized brain lesions found in routine management of children with newly diagnosed epilepsy and their interictal EEG findings. Total amount of 68 patients filled criteria for inclusion in the study that was performed at Neuropediatrics Department, Pediatric Hospital, University Clinical Center Sarajevo, or its outpatient clinic. There were 33 girls (48,5%) and 35 boys (51,5%). Average age at diagnosis of epilepsy was 3,5 years. Both neurological and neuropsychological examination in the moment of making diagnosis of epilepsy was normal in 27 (39,7%) patients, and showed some kind of delay or other neurological finding in 41 (60,3%). Brain MRI showed lesions that can be related to antenatal or perinatal events in most of the patients (ventricular dilation in 30,9%, delayed myelination and post-hypoxic changes in 27,9%). More than half of patients (55,9%) showed bilateral interictal epileptiform discharges on their EEGs, and further 14,7% had other kinds of bilateral abnormalities. Frequency of bilateral epileptic discharges showed statistically significant predominance on level of p<0,05. Cross tabulation between specific types of bilateral brain MRI lesions and EEG finding did not reveal significant type of EEG for assessed brain lesions. We conclude that there exists relationship between bilaterally localized brain MRI lesions and interictal bilateral epileptiform or nonspecific EEG findings in children with newly diagnosed epilepsies. These data are suggesting that in cases when they do not correlate there is a need for further investigation of seizure etiology.

Decreased anxiety- and depression-like behaviors and hyperactivity in a type 3 deiodinase-deficient mouse showing brain thyrotoxicosis and peripheral hypothyroidism.

PubMed

Stohn, J Patrizia; Martinez, M Elena; Hernandez, Arturo

2016-12-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 -/- mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 -/- mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 -/- mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. Copyright © 2016 Elsevier Ltd. All rights reserved.

Decreased Anxiety- and Depression-like Behaviors and Hyperactivity in a Type 3 Deiodinase-Deficient Mouse Showing Brain Thyrotoxicosis and Peripheral Hypothyroidism

PubMed Central

Stohn, J. Patrizia; Martinez, M. Elena; Hernandez, Arturo

2016-01-01

Hypo- and hyperthyroid states, as well as functional abnormalities in the hypothalamic-pituitary-thyroid axis have been associated with psychiatric conditions like anxiety and depression. However, the nature of this relationship is poorly understood since it is difficult to ascertain the thyroid status of the brain in humans. Data from animal models indicate that the brain exhibits efficient homeostatic mechanisms that maintain local levels of the active thyroid hormone, triiodothyronine (T3) within a narrow range. To better understand the consequences of peripheral and central thyroid status for mood-related behaviors, we used a mouse model of type 3 deiodinase (DIO3) deficiency (Dio3 −/− mouse). This enzyme inactivates thyroid hormone and is highly expressed in the adult central nervous system. Adult Dio3 −/− mice exhibit elevated levels of T3-dependent gene expression in the brain, despite peripheral hypothyroidism as indicated by low circulating levels of thyroxine and T3. Dio3 −/− mice of both sexes exhibit hyperactivity and significantly decreased anxiety-like behavior, as measured by longer time spent in the open arms of the elevated plus maze and in the light area of the light/dark box. During the tail suspension, they stayed immobile for a significantly shorter time than their wild-type littermates, suggesting decreased depression-like behavior. These results indicate that increased thyroid hormone in the brain, not necessarily in peripheral tissues, correlates with hyperactivity and with decreases in anxiety and depression-like behaviors. Our results also underscore the importance of DIO3 as a determinant of behavior by locally regulating the brain levels of thyroid hormone. PMID:27580013

A Milieu Molecule for TGF-β Required for Microglia Function in the Nervous System.

PubMed

Qin, Yan; Garrison, Brian S; Ma, Wenjiang; Wang, Rui; Jiang, Aiping; Li, Jing; Mistry, Meeta; Bronson, Roderick T; Santoro, Daria; Franco, Charlotte; Robinton, Daisy A; Stevens, Beth; Rossi, Derrick J; Lu, Chafen; Springer, Timothy A

2018-06-12

Extracellular proTGF-β is covalently linked to "milieu" molecules in the matrix or on cell surfaces and is latent until TGF-β is released by integrins. Here, we show that LRRC33 on the surface of microglia functions as a milieu molecule and enables highly localized, integrin-αVβ8-dependent TGF-β activation. Lrrc33 -/- mice lack CNS vascular abnormalities associated with deficiency in TGF-β-activating integrins but have microglia with a reactive phenotype and after 2 months develop ascending paraparesis with loss of myelinated axons and death by 5 months. Whole bone marrow transplantation results in selective repopulation of Lrrc33 -/- brains with WT microglia and halts disease progression. The phenotypes of WT and Lrrc33 -/- microglia in the same brain suggest that there is little spreading of TGF-β activated from one microglial cell to neighboring microglia. Our results suggest that interactions between integrin-bearing cells and cells bearing milieu molecule-associated TGF-β provide localized and selective activation of TGF-β. Copyright © 2018 Elsevier Inc. All rights reserved.

Three types of ependymal cells with intracellular calcium oscillation are characterized by distinct cilia beating properties.

PubMed

Liu, Tongyu; Jin, Xingjian; Prasad, Rahul M; Sari, Youssef; Nauli, Surya M

2014-09-01

Ependymal cells are multiciliated epithelial cells that line the ventricles in the adult brain. Abnormal function or structure of ependymal cilia has been associated with various neurological deficits. For the first time, we report three distinct ependymal cell types, I, II, and III, based on their unique ciliary beating frequency and beating angle. These ependymal cells have specific localizations within the third ventricle of the mouse brain. Furthermore, neither ependymal cell types nor their localizations are altered by aging. Our high-speed fluorescence imaging analysis reveals that these ependymal cells have an intracellular pacing calcium oscillation property. Our study further shows that alcohol can significantly repress the amplitude of calcium oscillation and the frequency of ciliary beating, resulting in an overall decrease in volume replacement by the cilia. Furthermore, the pharmacological agent cilostazol could differentially increase cilia beating frequency in type II, but not in type I or type III, ependymal cells. In summary, we provide the first evidence of three distinct types of ependymal cells with calcium oscillation properties. © 2014 Wiley Periodicals, Inc.

Inflammation and Alzheimer’s disease

PubMed Central

Akiyama, Haruhiko; Barger, Steven; Barnum, Scott; Bradt, Bonnie; Bauer, Joachim; Cole, Greg M.; Cooper, Neil R.; Eikelenboom, Piet; Emmerling, Mark; Fiebich, Berndt L.; Finch, Caleb E.; Frautschy, Sally; Griffin, W.S.T.; Hampel, Harald; Hull, Michael; Landreth, Gary; Lue, Lih–Fen; Mrak, Robert; Mackenzie, Ian R.; McGeer, Patrick L.; O’Banion, M. Kerry; Pachter, Joel; Pasinetti, Guilio; Plata–Salaman, Carlos; Rogers, Joseph; Rydel, Russell; Shen, Yong; Streit, Wolfgang; Strohmeyer, Ronald; Tooyoma, Ikuo; Van Muiswinkel, Freek L.; Veerhuis, Robert; Walker, Douglas; Webster, Scott; Wegrzyniak, Beatrice; Wenk, Gary; Wyss–Coray, Tony

2013-01-01

Inflammation clearly occurs in pathologically vulnerable regions of the Alzheimer’s disease (AD) brain, and it does so with the full complexity of local peripheral inflammatory responses. In the periphery, degenerating tissue and the deposition of highly insoluble abnormal materials are classical stimulants of inflammation. Likewise, in the AD brain damaged neurons and neurites and highly insoluble amyloid β peptide deposits and neurofibrillary tangles provide obvious stimuli for inflammation. Because these stimuli are discrete, microlocalized, and present from early preclinical to terminal stages of AD, local upregulation of complement, cytokines, acute phase reactants, and other inflammatory mediators is also discrete, microlocalized, and chronic. Cumulated over many years, direct and bystander damage from AD inflammatory mechanisms is likely to significantly exacerbate the very pathogenic processes that gave rise to it. Thus, animal models and clinical studies, although still in their infancy, strongly suggest that AD inflammation significantly contributes to AD pathogenesis. By better understanding AD inflammatory and immunoregulatory processes, it should be possible to develop anti-inflammatory approaches that may not cure AD but will likely help slow the progression or delay the onset of this devastating disorder. PMID:10858586

Subnetwork mining on functional connectivity network for classification of minimal hepatic encephalopathy.

PubMed

Zhang, Daoqiang; Tu, Liyang; Zhang, Long-Jiang; Jie, Biao; Lu, Guang-Ming

2018-06-01

Hepatic encephalopathy (HE), as a complication of cirrhosis, is a serious brain disease, which may lead to death. Accurate diagnosis of HE and its intermediate stage, i.e., minimal HE (MHE), is very important for possibly early diagnosis and treatment. Brain connectivity network, as a simple representation of brain interaction, has been widely used for the brain disease (e.g., HE and MHE) analysis. However, those studies mainly focus on finding disease-related abnormal connectivity between brain regions, although a large number of studies have indicated that some brain diseases are usually related to local structure of brain connectivity network (i.e., subnetwork), rather than solely on some single brain regions or connectivities. Also, mining such disease-related subnetwork is a challenging task because of the complexity of brain network. To address this problem, we proposed a novel frequent-subnetwork-based method to mine disease-related subnetworks for MHE classification. Specifically, we first mine frequent subnetworks from both groups, i.e., MHE patients and non-HE (NHE) patients, respectively. Then we used the graph-kernel based method to select the most discriminative subnetworks for subsequent classification. We evaluate our proposed method on a MHE dataset with 77 cirrhosis patients, including 38 MHE patients and 39 NHE patients. The results demonstrate that our proposed method can not only obtain the improved classification performance in comparison with state-of-the-art network-based methods, but also identify disease-related subnetworks which can help us better understand the pathology of the brain diseases.

Chronic cerebro-spinal venous insufficiency (CCSVI) and multiple sclerosis.

PubMed

Ghezzi, A; Comi, G; Federico, A

2011-02-01

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the CNS caused by the interplay of genetic and environmental factors. In the last years, it has been suggested that an abnormal venous drainage due to stenosis or malformation of the internal jugular and/or azygous veins may play a major pathogenetic role in MS. This abnormality called chronic cerebro-spinal venous insufficiency (CCSVI) could result in increased permeability of blood brain barrier, local iron deposition and secondary multifocal inflammation. In the present paper, literature data in favour and against this hypothesis are reported. A great variability of CCSVI has been found in both MS patients (ranging from 0 to 100%) and in control subjects (from 0 to 23%). This large variability is explained by methodological aspects, problems in assessing CCSVI, and differences among clinical series. It is urgent to perform appropriate epidemiological studies to define the possible relationship between CCSVI and MS.

The Sequelae of Acute Purulent Meningitis in Childhood

PubMed Central

Hutchison, Patricia A.; Kovacs, Michael C.

1963-01-01

Of a series of 122 children suffering from acute purulent meningitis at the Children's Hospital, Winnipeg, in the years 1952-56, 12 (9.8%) succumbed, all deaths occurring in those 12 months of age or less. Fortyone of the survivors were re-studied 2.5 to 7.5 years after their acute illness to assess the nature and incidence of sequelae, the relationship of sequelae to the severity of the acute illness, and the correlation between the various methods of identifying sequelae. Five children exhibited psychiatric evidence of organic brain damage; seven, neurological abnormality; 11, electroencephalographic abnormality. Three had defective intelligence and nine psychological test evidence of organic brain damage. Children with sequelae tended to have several abnormal test results, the total number with neuropsychiatric and/or psychological sequelae being 11 (26%). There was a positive correlation between the severity of the acute illness and the presence of neuropsychiatric sequelae; also between neuropsychiatric sequelae, defective intelligence and psychological evidence of brain damage. No correlation existed between the electroencephalographic abnormality and neuropsychiatric defect. PMID:13955939

Multifaceted impairments in impulsivity and brain structural abnormalities in opioid dependence and abstinence.

PubMed

Tolomeo, S; Gray, S; Matthews, K; Steele, J D; Baldacchino, A

2016-10-01

Chronic opioid exposure, as a treatment for a variety of disorders or as drug of misuse, is common worldwide, but behavioural and brain abnormalities remain under-investigated. Only a small percentage of patients who receive methadone maintenance treatment (MMT) for previous heroin misuse eventually achieve abstinence and studies on such patients are rare. The Cambridge Neuropsychological Test Automated Battery and T1 weighted magnetic resonance imaging (MRI) were used to study a cohort of 122 male individuals: a clinically stable opioid-dependent patient group receiving MMT (n = 48), an abstinent previously MMT maintained group (ABS) (n = 24) and healthy controls (n = 50). Stable MMT participants deliberated longer and placed higher bets earlier in the Cambridge Gambling Task (CGT) and showed impaired strategic planning compared with healthy controls. In contrast, ABS participants showed impairment in choosing the least likely outcome, delay aversion and risk adjustment on the CGT, and exhibited non-planning impulsivity compared with controls. MMT patients had widespread grey matter reductions in the orbitomedial prefrontal cortex, caudate, putamen and globus pallidus. In contrast, ABS participants showed midbrain-thalamic grey matter reductions. A higher methadone dose at the time of scanning was associated with a smaller globus pallidus in the MMT group. Our findings support an interpretation of heightened impulsivity in patients receiving MMT. Widespread structural brain abnormalities in the MMT group and reduced brain structural abnormality with abstinence suggest benefit of cessation of methadone intake. We suggest that a longitudinal study is required to determine whether abstinence improves abnormalities, or patients who achieve abstinence have reduced abnormalities before methadone cessation.

Grey matter volume and thickness abnormalities in young people with a history of childhood abuse.

PubMed

Lim, L; Hart, H; Mehta, M; Worker, A; Simmons, A; Mirza, K; Rubia, K

2018-04-01

Childhood abuse is associated with abnormalities in brain structure and function. Few studies have investigated abuse-related brain abnormalities in medication-naïve, drug-free youth that also controlled for psychiatric comorbidities by inclusion of a psychiatric control group, which is crucial to disentangle the effects of abuse from those associated with the psychiatric conditions. Cortical volume (CV), cortical thickness (CT) and surface area (SA) were measured in 22 age- and gender-matched medication-naïve youth (aged 13-20) exposed to childhood abuse, 19 psychiatric controls matched for psychiatric diagnoses and 27 healthy controls. Both region-of-interest (ROI) and whole-brain analyses were conducted. For the ROI analysis, the childhood abuse group compared with healthy controls only, had significantly reduced CV in bilateral cerebellum and reduced CT in left insula and right lateral orbitofrontal cortex (OFC). At the whole-brain level, relative to healthy controls, the childhood abuse group showed significantly reduced CV in left lingual, pericalcarine, precuneus and superior parietal gyri, and reduced CT in left pre-/postcentral and paracentral regions, which furthermore correlated with greater abuse severity. They also had increased CV in left inferior and middle temporal gyri relative to healthy controls. Abnormalities in the precuneus, temporal and precentral regions were abuse-specific relative to psychiatric controls, albeit at a more lenient level. Groups did not differ in SA. Childhood abuse is associated with widespread structural abnormalities in OFC-insular, cerebellar, occipital, parietal and temporal regions, which likely underlie the abnormal affective, motivational and cognitive functions typically observed in this population.

Quantitative analysis of brain magnetic resonance imaging for hepatic encephalopathy

NASA Astrophysics Data System (ADS)

Syh, Hon-Wei; Chu, Wei-Kom; Ong, Chin-Sing

1992-06-01

High intensity lesions around ventricles have recently been observed in T1-weighted brain magnetic resonance images for patients suffering hepatic encephalopathy. The exact etiology that causes magnetic resonance imaging (MRI) gray scale changes has not been totally understood. The objective of our study was to investigate, through quantitative means, (1) the amount of changes to brain white matter due to the disease process, and (2) the extent and distribution of these high intensity lesions, since it is believed that the abnormality may not be entirely limited to the white matter only. Eleven patients with proven haptic encephalopathy and three normal persons without any evidence of liver abnormality constituted our current data base. Trans-axial, sagittal, and coronal brain MRI were obtained on a 1.5 Tesla scanner. All processing was carried out on a microcomputer-based image analysis system in an off-line manner. Histograms were decomposed into regular brain tissues and lesions. Gray scale ranges coded as lesion were then brought back to original images to identify distribution of abnormality. Our results indicated the disease process involved pallidus, mesencephalon, and subthalamic regions.

Neonatal brain structure on MRI and diffusion tensor imaging, sex, and neurodevelopment in very-low-birthweight preterm children.

PubMed

Rose, Jessica; Butler, Erin E; Lamont, Lauren E; Barnes, Patrick D; Atlas, Scott W; Stevenson, David K

2009-07-01

The neurological basis of an increased incidence of cerebral palsy (CP) in preterm males is unknown. This study examined neonatal brain structure on magnetic resonance imaging (MRI) and diffusion tensor imaging (DTI) at term-equivalent age, sex, and neurodevelopment at 1 year 6 months on the basis of the Amiel-Tison neurological examination, Gross Motor Function Classification System, and Bayley Scales of Infant Development in 78 very-low-birthweight preterm children (41 males, 37 females; mean gestational age 27.6 wks, SD 2.5; mean birthweight 1021 g, SD 339). Brain abnormalities on MRI and DTI were not different between males and females except in the splenium of the corpus callosum, where males had lower DTI fractional anisotropy (p=0.025) and a higher apparent diffusion coefficient (p=0.013), indicating delayed splenium development. In the 26 infants who were at higher risk on the basis of DTI, males had more abnormalities on MRI (p=0.034) and had lower fractional anisotropy and a higher apparent diffusion coefficient in the splenium (p=0.049; p=0.025) and right posterior limb of the internal capsule (PLIC; p=0.003; p=0.033). Abnormal neurodevelopment was more common in males (n=9) than in females (n=2; p=0.036). Children with abnormal neurodevelopment had more abnormalities on MRI (p=0.014) and reduced splenium and right PLIC fractional anisotropy (p=0.001; p=0.035). In children with abnormal neurodevelopment, right PLIC fractional anisotropy was lower than left (p=0.035), whereas in those with normal neurodevelopment right PLIC fractional anisotropy was higher than left (p=0.001). Right PLIC fractional anisotropy correlated to neurodevelopment (rho=0.371, p=0.002). Logistic regression predicted neurodevelopment with 94% accuracy; only right PLIC fractional anisotropy was a significant logistic coefficient. Results indicate that the higher incidence of abnormal neurodevelopment in preterm males relates to greater incidence and severity of brain abnormalities, including reduced PLIC and splenium development.

A network analysis of ¹⁵O-H₂O PET reveals deep brain stimulation effects on brain network of Parkinson's disease.

PubMed

Park, Hae-Jeong; Park, Bumhee; Kim, Hae Yu; Oh, Maeng-Keun; Kim, Joong Il; Yoon, Misun; Lee, Jong Doo; Chang, Jin Woo

2015-05-01

As Parkinson's disease (PD) can be considered a network abnormality, the effects of deep brain stimulation (DBS) need to be investigated in the aspect of networks. This study aimed to examine how DBS of the bilateral subthalamic nucleus (STN) affects the motor networks of patients with idiopathic PD during motor performance and to show the feasibility of the network analysis using cross-sectional positron emission tomography (PET) images in DBS studies. We obtained [¹⁵O]H₂O PET images from ten patients with PD during a sequential finger-to-thumb opposition task and during the resting state, with DBS-On and DBS-Off at STN. To identify the alteration of motor networks in PD and their changes due to STN-DBS, we applied independent component analysis (ICA) to all the cross-sectional PET images. We analysed the strength of each component according to DBS effects, task effects and interaction effects. ICA blindly decomposed components of functionally associated distributed clusters, which were comparable to the results of univariate statistical parametric mapping. ICA further revealed that STN-DBS modifies usage-strengths of components corresponding to the basal ganglia-thalamo-cortical circuits in PD patients by increasing the hypoactive basal ganglia and by suppressing the hyperactive cortical motor areas, ventrolateral thalamus and cerebellum. Our results suggest that STN-DBS may affect not only the abnormal local activity, but also alter brain networks in patients with PD. This study also demonstrated the usefulness of ICA for cross-sectional PET data to reveal network modifications due to DBS, which was not observable using the subtraction method.

Altered functional connectivity in early Alzheimer's disease: a resting-state fMRI study.

PubMed

Wang, Kun; Liang, Meng; Wang, Liang; Tian, Lixia; Zhang, Xinqing; Li, Kuncheng; Jiang, Tianzi

2007-10-01

Previous studies have led to the proposal that patients with Alzheimer's disease (AD) may have disturbed functional connectivity between different brain regions. Furthermore, recent resting-state functional magnetic resonance imaging (fMRI) studies have also shown that low-frequency (<0.08 Hz) fluctuations (LFF) of the blood oxygenation level-dependent signals were abnormal in several brain areas of AD patients. However, few studies have investigated disturbed LFF connectivity in AD patients. By using resting-state fMRI, this study sought to investigate the abnormal functional connectivities throughout the entire brain of early AD patients, and analyze the global distribution of these abnormalities. For this purpose, the authors divided the whole brain into 116 regions and identified abnormal connectivities by comparing the correlation coefficients of each pair. Compared with healthy controls, AD patients had decreased positive correlations between the prefrontal and parietal lobes, but increased positive correlations within the prefrontal lobe, parietal lobe, and occipital lobe. The AD patients also had decreased negative correlations (closer to zero) between two intrinsically anti-correlated networks that had previously been found in the resting brain. By using resting-state fMRI, our results supported previous studies that have reported an anterior-posterior disconnection phenomenon and increased within-lobe functional connectivity in AD patients. In addition, the results also suggest that AD may disturb the correlation/anti-correlation effect in the two intrinsically anti-correlated networks. Wiley-Liss, Inc.

Cerebral blood perfusion after treatment with zolpidem and flumazenil in the baboon.

PubMed

Clauss, Ralf P; Dormehl, Irene C; Kilian, Elmaré; Louw, Werner K A; Nel, Wally H; Oliver, Douglas W

2002-01-01

Previous studies have shown that zolpidem (CAS 82626-48-0) can lead to improved perfusion in damaged brain tissue. Zolpidem belongs to the imidazopyridine chemical class and it illicits its pharmacological action via the gamma-aminobutyric acid (GABA) receptor system through stimulation of particularly the omega 1 receptors and to a lesser extent omega 2 receptors. Previously it was reported that no cerebral blood flow effects were observed in normal baboons after treatment with zolpidem, whereas an asymmetric regional increase in cerebral blood flow was observed in a neurologically abnormal baboon. In this study, the effect of a combination of the benzodiazepine receptor antagonist flumazenil (CAS 78755-81-4) and zolpidem on brain perfusion was examined by the 99mTc-hexamethyl-propylene amine oxime (99mTc-HMPAO) split dose brain single photon emission computed tomography (SPECT). Four normal baboons and the neurologically abnormal baboon from the previous zolpidem study were examined. In the current study the asymmetric changes observed after zolpidem--only treatment in the abnormal baboon was attenuated by flumazenil intervention. A decreased brain blood flow was observed after combination treatment of zolpidem and flumazenil in the normal baboons. The involvement of the omega receptors is suggested by these results. Up- or down-regulation of omega receptors may also contribute to the observed responses in the abnormal baboon and a brain injured patient.

Abnormal brain magnetic resonance imaging in two patients with Smith-Magenis syndrome.

PubMed

Maya, Idit; Vinkler, Chana; Konen, Osnat; Kornreich, Liora; Steinberg, Tamar; Yeshaya, Josepha; Latarowski, Victoria; Shohat, Mordechai; Lev, Dorit; Baris, Hagit N

2014-08-01

Smith-Magenis syndrome (SMS) is a clinically recognizable contiguous gene syndrome ascribed to an interstitial deletion in chromosome 17p11.2. Seventy percent of SMS patients have a common deletion interval spanning 3.5 megabases (Mb). Clinical features of SMS include characteristic mild dysmorphic features, ocular anomalies, short stature, brachydactyly, and hypotonia. SMS patients have a unique neurobehavioral phenotype that includes intellectual disability, self-injurious behavior and severe sleep disturbance. Little has been reported in the medical literature about anatomical brain anomalies in patients with SMS. Here we describe two patients with SMS caused by the common deletion in 17p11.2 diagnosed using chromosomal microarray (CMA). Both patients had a typical clinical presentation and abnormal brain magnetic resonance imaging (MRI) findings. One patient had subependymal periventricular gray matter heterotopia, and the second had a thin corpus callosum, a thin brain stem and hypoplasia of the cerebellar vermis. This report discusses the possible abnormal MRI images in SMS and reviews the literature on brain malformations in SMS. Finally, although structural brain malformations in SMS patients are not a common feature, we suggest baseline routine brain imaging in patients with SMS in particular, and in patients with chromosomal microdeletion/microduplication syndromes in general. Structural brain malformations in these patients may affect the decision-making process regarding their management. © 2014 Wiley Periodicals, Inc.

Ewing's sarcoma of the cranial vault: a case report.

PubMed

Feki, Jihene; Guermazi, Zeineb; Kammoun, Brahim; Khanfir, Afef; Toumi, Nabil; Boudawara, Tahiya; Boudawara, Zaher; Daoud, Jamel; Frikha, Mounir

2017-12-01

Ewing's sarcoma is a malignant tumor that mainly affects young patients. It represents 10% of primary malignant tumors of the bone and 3% of malignant tumors of the child. Cranial localization is extremely rare representing less than 1% of all the localizations. We report a case of a 10-year-old girl who presented with an intracranial hypertension syndrome with left parietal mass of progressive installation. The X-ray skull showed a lytic lesion with irregular margins involving the left parietal bone. Brain magnetic resonance imaging revealed extensive parietal bone destruction involving both the inner and outer tables. The girl was operated in emergency. Histological examination concluded to Ewing's Sarcoma. The resection was incomplete (R1). The girl received induction's chemotherapy. The cerebral scanner evaluation showed no abnormalities. Then, she received consolidation's chemotherapy with concomitant local radiation therapy. Currently, the girl is in complete remission with a seven-month decline.

Compulsive masturbation and chronic penile lymphedema.

PubMed

Calabrò, Rocco Salvatore; Galì, Alessandro; Marino, Silvia; Bramanti, Placido

2012-06-01

Chronic penile lymphedema arises from the abnormal retention of lymphatic fluid in the subcutaneous tissues and may be secondary to local and systemic medical conditions such as sexually transmitted diseases, filariasis, malignancy, local radiotherapy, and surgery. This case report aims to consider compulsive masturbation as a possible cause of chronic penile edema. A 40-year-old man was referred to our institute for behavioral disturbance, including compulsive masturbation. Neuropsychiatric evaluation showed moderate mental retardation, mild dysarthria and limb incoordination, anxiety, depressed mood, and impulse dyscontrol. Brain MRI pointed out diffuse white matter lesions. Urogenital examination revealed an uncircumcised penis with non-tender edema of the shaft and prepuce with areas of lichenification. Since the most common local and systemic causes of edema were excluded, chronic penile edema due to compulsive masturbation was diagnosed and the compulsive behavior treated with an antidepressant and low-dose neuroleptics. Compulsive masturbation should be taken into account when counselling patients with penile edema.

Evidence for brain glucose dysregulation in Alzheimer's disease.

PubMed

An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

2018-03-01

It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

Abnormal cholesterol is associated with prefrontal white matter abnormalities among obese adults, a diffusion tensor imaging study

PubMed Central

Cohen, Jessica I.; Cazettes, Fanny; Convit, Antonio

2011-01-01

The brain is the most cholesterol-rich organ in the body. Although most of the cholesterol in the brain is produced endogenously, some studies suggest that systemic cholesterol may be able to enter the brain. We investigated whether abnormal cholesterol profiles correlated with diffusion-tensor-imaging-based estimates of white matter microstructural integrity of lean and overweight/obese (o/o) adults. Twenty-two lean and 39 obese adults underwent magnetic resonance imaging, kept a 3-day food diary, and had a standardized assessment of fasting blood lipids. The lean group ate less cholesterol rich food than o/o although both groups ate equivalent servings of food per day. Voxelwise correlational analyses controlling for age, diabetes, and white matter hyperintensities, resulted in two significant clusters of negative associations between abnormal cholesterol profile and fractional anisotropy, located in the left and right prefrontal lobes. When the groups were split, the lean subjects showed no associations, whereas the o/o group expanded the association to three significant clusters, still in the frontal lobes. These findings suggest that cholesterol profile abnormalities may explain some of the reductions in white matter microstructural integrity that are reported in obesity. PMID:22163070

Brain MRI in neuropsychiatric lupus: associations with the 1999 ACR case definitions.

PubMed

Jeong, Hae Woong; Her, Minyoung; Bae, Jong Seok; Kim, Seong-Kyu; Lee, Sung Won; Kim, Ho Kyun; Kim, Dongyook; Park, Nayoung; Chung, Won Tae; Lee, Sang Yeob; Choe, Jung-Yoon; Kim, In Joo

2015-05-01

The purpose of this study was to identify the characteristic magnetic resonance imaging (MRI) findings in neuropsychiatric systemic lupus erythematosus (NPSLE) and to investigate the association between MRI findings and neuropsychiatric manifestations in SLE. Brain MRIs with a diagnosis of SLE from 2002 to 2013 from three tertiary university hospitals were screened. All clinical manifestations evaluated by brain MRI were retrospectively reviewed. If the clinical manifestations were compatible with the 1999 NPSLE American College of Rheumatology (ACR) nomenclature and case definitions, the brain MRIs were assessed for the presence of white matter hyperintensities, gray matter hyperintensities, parenchymal defects, atrophy, enhancement, and abnormalities in diffusion-weighted images (DWI). The number, size, and location of each lesion were evaluated. The neuropsychiatric manifestation of each brain MRI was classified according to the 1999 ACR NPSLE case definitions. The associations between MRI findings and NPSLE manifestations were examined. In total, 219 brain MRIs with a diagnosis of SLE were screened, and 133 brain MRIs met the inclusion criteria for NPSLE. The most common MRI abnormality was white matter hyperintensities, which were observed in 76 MRIs (57.1 %). Gray matter hyperintensities were observed in 41 MRIs (30.8 %). Parenchymal defects were found in 31 MRIs (23.3 %), and atrophy was detected in 20 MRIs (15.0 %). Patients who had seizures were more associated with gray matter hyperintensities than patients with other neuropsychiatric manifestations. Patients with cerebrovascular disease were more associated with gray matter hyperintensity, parenchymal defects, and abnormal DWI than patients with other neuropsychiatric manifestations. In addition to white matter hyperintensities, which were previously known as SLE findings, we also noted the presence of gray matter hyperintensities, parenchymal defects, and abnormal DWI in a substantial portion of SLE patients, particularly in those with cerebrovascular disease or seizures.

Changes in motor function, cognition, and emotion-related behavior after right hemispheric intracerebral hemorrhage in various brain regions of mouse.

PubMed

Zhu, Wei; Gao, Yufeng; Wan, Jieru; Lan, Xi; Han, Xiaoning; Zhu, Shanshan; Zang, Weidong; Chen, Xuemei; Ziai, Wendy; Hanley, Daniel F; Russo, Scott J; Jorge, Ricardo E; Wang, Jian

2018-03-01

Intracerebral hemorrhage (ICH) is a detrimental type of stroke. Mouse models of ICH, induced by collagenase or blood infusion, commonly target striatum, but not other brain sites such as ventricular system, cortex, and hippocampus. Few studies have systemically investigated brain damage and neurobehavioral deficits that develop in animal models of ICH in these areas of the right hemisphere. Therefore, we evaluated the brain damage and neurobehavioral dysfunction associated with right hemispheric ICH in ventricle, cortex, hippocampus, and striatum. The ICH model was induced by autologous whole blood or collagenase VII-S (0.075 units in 0.5 µl saline) injection. At different time points after ICH induction, mice were assessed for brain tissue damage and neurobehavioral deficits. Sham control mice were used for comparison. We found that ICH location influenced features of brain damage, microglia/macrophage activation, and behavioral deficits. Furthermore, the 24-point neurologic deficit scoring system was most sensitive for evaluating locomotor abnormalities in all four models, especially on days 1, 3, and 7 post-ICH. The wire-hanging test was useful for evaluating locomotor abnormalities in models of striatal, intraventricular, and cortical ICH. The cylinder test identified locomotor abnormalities only in the striatal ICH model. The novel object recognition test was effective for evaluating recognition memory dysfunction in all models except for striatal ICH. The tail suspension test, forced swim test, and sucrose preference test were effective for evaluating emotional abnormality in all four models but did not correlate with severity of brain damage. These results will help to inform future preclinical studies of ICH outcomes. Copyright © 2018 Elsevier Inc. All rights reserved.

A systematic review of visual processing and associated treatments in body dysmorphic disorder.

PubMed

Beilharz, F; Castle, D J; Grace, S; Rossell, S L

2017-07-01

Recent advances in body dysmorphic disorder (BDD) have explored abnormal visual processing, yet it is unclear how this relates to treatment. The aim of this study was to summarize our current understanding of visual processing in BDD and review associated treatments. The literature was collected through PsycInfo and PubMed. Visual processing articles were included if written in English after 1970, had a specific BDD group compared to healthy controls and were not case studies. Due to the lack of research regarding treatments associated with visual processing, case studies were included. A number of visual processing abnormalities are present in BDD, including face recognition, emotion identification, aesthetics, object recognition and gestalt processing. Differences to healthy controls include a dominance of detailed local processing over global processing and associated changes in brain activation in visual regions. Perceptual mirror retraining and some forms of self-exposure have demonstrated improved treatment outcomes, but have not been examined in isolation from broader treatments. Despite these abnormalities in perception, particularly concerning face and emotion recognition, few BDD treatments attempt to specifically remediate this. The development of a novel visual training programme which addresses these widespread abnormalities may provide an effective treatment modality. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Excessive homozygosity identified by chromosomal microarray at a known GCDH mutation locus correlates with brain MRI abnormalities in an infant with glutaric aciduria.

PubMed

Peer-Zada, Abdul Ali; Al-Asmari, Ali M

2017-08-01

Herein, we report a conceptually novel clinical case highlighting the diagnostic implications of excessive homozygosity and its correlation with brain MRI abnormalities in an infant with GA1. The case also points a need for an extra amount of caution to be exercised when evaluating patients with "negative exomes."

Gulf War Illness as a Brain Autoimmune Disorder

DTIC Science & Technology

2017-10-01

autoimmune disorders, to determine the extent to which GWI reflects autoimmune abnormalities . Altogether, our study will improve knowledge of GWI...University of Minnesota Medical School, Minneapolis, MN 55455, USA d Department of Psychology , University of Minnesota, Minneapolis, MN 55455, USA e...gain further knowledge regarding the nature of GWI brain abnormality . We studied a total of 962 participants from a healthy control population (N

Volume estimation of brain abnormalities in MRI data

NASA Astrophysics Data System (ADS)

Suprijadi, Pratama, S. H.; Haryanto, F.

2014-02-01

The abnormality of brain tissue always becomes a crucial issue in medical field. This medical condition can be recognized through segmentation of certain region from medical images obtained from MRI dataset. Image processing is one of computational methods which very helpful to analyze the MRI data. In this study, combination of segmentation and rendering image were used to isolate tumor and stroke. Two methods of thresholding were employed to segment the abnormality occurrence, followed by filtering to reduce non-abnormality area. Each MRI image is labeled and then used for volume estimations of tumor and stroke-attacked area. The algorithms are shown to be successful in isolating tumor and stroke in MRI images, based on thresholding parameter and stated detection accuracy.

White matter microstructure and cognitive decline in metabolic syndrome: a review of diffusion tensor imaging.

PubMed

Alfaro, Freddy J; Gavrieli, Anna; Saade-Lemus, Patricia; Lioutas, Vasileios-Arsenios; Upadhyay, Jagriti; Novak, Vera

2018-01-01

Metabolic syndrome is a cluster of cardiovascular risk factors defined by the presence of abdominal obesity, glucose intolerance, hypertension and/or dyslipidemia. It is a major public health epidemic worldwide, and a known risk factor for the development of cognitive dysfunction and dementia. Several studies have demonstrated a positive association between the presence of metabolic syndrome and worse cognitive outcomes, however, evidence of brain structure pathology is limited. Diffusion tensor imaging has offered new opportunities to detect microstructural white matter changes in metabolic syndrome, and a possibility to detect associations between functional and structural abnormalities. This review analyzes the impact of metabolic syndrome on white matter microstructural integrity, brain structure abnormalities and their relationship to cognitive function. Each of the metabolic syndrome components exerts a specific signature of white matter microstructural abnormalities. Metabolic syndrome and its components exert both additive/synergistic, as well as, independent effects on brain microstructure thus accelerating brain aging and cognitive decline. Copyright © 2017 Elsevier Inc. All rights reserved.

Prenatal diagnosis of brain abnormalities in Wolf-Hirschhorn (4p-) syndrome.

PubMed

De Keersmaecker, B; Albert, M; Hillion, Y; Ville, Y

2002-05-01

Although there have been occasional reports of prenatal diagnosis of this syndrome, most cases are diagnosed postnatally. The objective was to evaluate the presence of brain abnormalities in the prenatal diagnosis of Wolf-Hirschhorn syndrome. Prenatal ultrasound and MRI examination of the fetal brain were performed in a case of Wolf-Hirschhorn syndrome. A comprehensive review of Wolf-Hirschhorn syndrome reported between 1960 and 2000 in the literature was carried out. The late diagnosis of a growth-retarded fetus with normal amniotic fluid volume, normal Doppler and negative infection screen calls for a detailed examination of the fetal brain and heart. Multifocal white matter lesions and periventricular cystic changes, which are often attributed to perinatal distress, are possible prenatal features causing suspicion of 4p- syndrome in an IUGR fetus. Subtle abnormalities on ultrasound may suggest a chromosomal problem. Standard cytogenetics cannot always demonstrate a microdeletion. High-resolution banding and molecular analysis can help to confirm the diagnosis. Copyright 2002 John Wiley & Sons, Ltd.

Brain stem and inner ear abnormalities in children with auditory neuropathy spectrum disorder and cochlear nerve deficiency.

PubMed

Huang, B Y; Roche, J P; Buchman, C A; Castillo, M

2010-11-01

Cranial abnormalities, including CND, are common in children with ANSD. The purpose of this study was to assess whether CND is associated with brain or inner ear abnormalities in a cohort of children with ANSD. Two neuroradiologists retrospectively reviewed cranial MR imaging examinations in 103 children with ANSD. Brain, cochlear nerve, and temporal bone abnormalities were described and tabulated. Findings were stratified on the basis of the presence and laterality of CND, and differences in the presence of associated inner ear or intracranial abnormalities were assessed by using 2-tailed Fisher exact tests. CND was identified in 33.0% of children and 26.9% of ears with ANSD. Significantly more patients with bilateral CND had intracranial abnormalities than those with unilateral CND (60.0% versus 15.8%; P = .012). Forty percent of patients with bilateral CND, 0% of patients with unilateral CND, and 10.1% of those without CND demonstrated hindbrain malformations. Patients with bilateral CND were more likely to demonstrate hindbrain malformations than patients with normal nerves (P = .01) or unilateral CND (P = .004). Labyrinthine abnormalities were significantly more common in patients with bilateral CND than in those without CND (P ≤ .001). Cochlear anomalies were more common in patients with bilateral versus unilateral CND (P = .01). IAC and cochlear aperture stenosis were more common in those with unilateral and bilateral CND than those without CND (both P < .001). Cochlear and hindbrain abnormalities are significantly more common among patients with ANSD with bilateral CND compared with those with at least 1 intact cochlear nerve.

Functional brain networks in Alzheimer's disease: EEG analysis based on limited penetrable visibility graph and phase space method

NASA Astrophysics Data System (ADS)

Wang, Jiang; Yang, Chen; Wang, Ruofan; Yu, Haitao; Cao, Yibin; Liu, Jing

2016-10-01

In this paper, EEG series are applied to construct functional connections with the correlation between different regions in order to investigate the nonlinear characteristic and the cognitive function of the brain with Alzheimer's disease (AD). First, limited penetrable visibility graph (LPVG) and phase space method map single EEG series into networks, and investigate the underlying chaotic system dynamics of AD brain. Topological properties of the networks are extracted, such as average path length and clustering coefficient. It is found that the network topology of AD in several local brain regions are different from that of the control group with no statistically significant difference existing all over the brain. Furthermore, in order to detect the abnormality of AD brain as a whole, functional connections among different brain regions are reconstructed based on similarity of clustering coefficient sequence (CCSS) of EEG series in the four frequency bands (delta, theta, alpha, and beta), which exhibit obvious small-world properties. Graph analysis demonstrates that for both methodologies, the functional connections between regions of AD brain decrease, particularly in the alpha frequency band. AD causes the graph index complexity of the functional network decreased, the small-world properties weakened, and the vulnerability increased. The obtained results show that the brain functional network constructed by LPVG and phase space method might be more effective to distinguish AD from the normal control than the analysis of single series, which is helpful for revealing the underlying pathological mechanism of the disease.

Understanding principles of integration and segregation using whole-brain computational connectomics: implications for neuropsychiatric disorders

PubMed Central

Lord, Louis-David; Stevner, Angus B.; Kringelbach, Morten L.

2017-01-01

To survive in an ever-changing environment, the brain must seamlessly integrate a rich stream of incoming information into coherent internal representations that can then be used to efficiently plan for action. The brain must, however, balance its ability to integrate information from various sources with a complementary capacity to segregate information into modules which perform specialized computations in local circuits. Importantly, evidence suggests that imbalances in the brain's ability to bind together and/or segregate information over both space and time is a common feature of several neuropsychiatric disorders. Most studies have, however, until recently strictly attempted to characterize the principles of integration and segregation in static (i.e. time-invariant) representations of human brain networks, hence disregarding the complex spatio-temporal nature of these processes. In the present Review, we describe how the emerging discipline of whole-brain computational connectomics may be used to study the causal mechanisms of the integration and segregation of information on behaviourally relevant timescales. We emphasize how novel methods from network science and whole-brain computational modelling can expand beyond traditional neuroimaging paradigms and help to uncover the neurobiological determinants of the abnormal integration and segregation of information in neuropsychiatric disorders. This article is part of the themed issue ‘Mathematical methods in medicine: neuroscience, cardiology and pathology’. PMID:28507228

The Gini coefficient: a methodological pilot study to assess fetal brain development employing postmortem diffusion MRI.

PubMed

Viehweger, Adrian; Riffert, Till; Dhital, Bibek; Knösche, Thomas R; Anwander, Alfred; Stepan, Holger; Sorge, Ina; Hirsch, Wolfgang

2014-10-01

Diffusion-weighted imaging (DWI) is important in the assessment of fetal brain development. However, it is clinically challenging and time-consuming to prepare neuromorphological examinations to assess real brain age and to detect abnormalities. To demonstrate that the Gini coefficient can be a simple, intuitive parameter for modelling fetal brain development. Postmortem fetal specimens(n = 28) were evaluated by diffusion-weighted imaging (DWI) on a 3-T MRI scanner using 60 directions, 0.7-mm isotropic voxels and b-values of 0, 150, 1,600 s/mm(2). Constrained spherical deconvolution (CSD) was used as the local diffusion model. Fractional anisotropy (FA), apparent diffusion coefficient (ADC) and complexity (CX) maps were generated. CX was defined as a novel diffusion metric. On the basis of those three parameters, the Gini coefficient was calculated. Study of fetal brain development in postmortem specimens was feasible using DWI. The Gini coefficient could be calculated for the combination of the three diffusion parameters. This multidimensional Gini coefficient correlated well with age (Adjusted R(2) = 0.59) between the ages of 17 and 26 gestational weeks. We propose a new method that uses an economics concept, the Gini coefficient, to describe the whole brain with one simple and intuitive measure, which can be used to assess the brain's developmental state.

[MRI in congenital nystagmus].

PubMed

Denis, D; Girard, N; Toesca, E; Zanin, E; Gambarelli, N; Lebranchu, P; Mancini, J

2010-03-01

Congenital nystagmus (CN) that is present by the age of 3 months is the most common form of nystagmus in childhood. We present a prospective study (2001-2008) in which we report imaging findings in 48 children with CN. Twenty-six boys and 22 girls with CN underwent a complete ophthalmologic assessment and a cerebral MRI (mean age of examination under general anesthesia: 11 months). Three CN groups were formed: neurologic (n=27), sensory visual disturbance (n=14), and isolated (n=7). Cerebral MRI was interpreted by the same pediatric neuroradiologist (NG). Of the children studied, 98 % were born at term. The MRI abnormalities were classified as morphologic abnormalities (malformative or nonmalformative) and as signal abnormalities. The location of brain abnormalities was within the posterior fossa, (brain stem, cerebellum, dental nuclei, cisterna magna) and the cerebral hemisphere (white matter, perivascular spaces, midline commissures, basal ganglia). Pendular nystagmus was prevalent in sensory and neurologic nystagmus. On fundus examination, optic disc abnormalities were present in 70 % (19) of neurologic CN and associated with white matter abnormalities of the optic radiations in 40 % of cases. On MRI, malformative morphologic abnormalities were present in 27 cases, nonmalformative abnormalities were found in 67, and signal abnormalities in 68. Within the brain stem, signal abnormalities were found as a cockade appearance of the posterior pons in the reticular regions (neurologic n=14, sensory n=6, isolated n=3). Other bright (most frequent) signal abnormalities were found within the dentate nuclei of the posterior fossa (neurologic n=10, sensory n=3, isolated n=3) and the cerebral white matter (neurologic n=17, sensory n=7, isolated n=5) of which 24 (neurologic n=15, sensory n=5, isolated n=4) involved the optic radiations. Most of these abnormalities were related and were seen most frequently in neurologic nystagmus. The most frequent association was signal abnormalities of the white matter, ventricular dilatation, and dilatation of the perivascular spaces (60.4 %) (neurologic n=13, sensory n=6). This study showed the fundamental contribution of the cerebral MRI in CN. Cerebral abnormalities were found at the pathways for ocular motility, particularly at the saccadic pathways.

Segmentation of magnetic resonance images using fuzzy algorithms for learning vector quantization.

PubMed

Karayiannis, N B; Pai, P I

1999-02-01

This paper evaluates a segmentation technique for magnetic resonance (MR) images of the brain based on fuzzy algorithms for learning vector quantization (FALVQ). These algorithms perform vector quantization by updating all prototypes of a competitive network through an unsupervised learning process. Segmentation of MR images is formulated as an unsupervised vector quantization process, where the local values of different relaxation parameters form the feature vectors which are represented by a relatively small set of prototypes. The experiments evaluate a variety of FALVQ algorithms in terms of their ability to identify different tissues and discriminate between normal tissues and abnormalities.

Theories of autism.

PubMed

Levy, Florence

2007-11-01

The purpose of the present paper was to review psychological theories of autism, and to integrate these theories with neurobiological findings. Cognitive, theory of mind, language and coherence theories were identified, and briefly reviewed. Psychological theories were found not to account for the rigid/repetitive behaviours universally described in autistic subjects, and underlying neurobiological systems were identified. When the developing brain encounters constrained connectivity, it evolves an abnormal organization, the features of which may be best explained by a developmental failure of neural connectivity, where high local connectivity develops in tandem with low long-range connectivity, resulting in constricted repetitive behaviours.

A spectroscopic approach toward depression diagnosis: local metabolism meets functional connectivity.

PubMed

Demenescu, Liliana Ramona; Colic, Lejla; Li, Meng; Safron, Adam; Biswal, B; Metzger, Coraline Danielle; Li, Shijia; Walter, Martin

2017-03-01

Abnormal anterior insula (AI) response and functional connectivity (FC) is associated with depression. In addition to clinical features, such as severity, AI FC and its metabolism further predicted therapeutic response. Abnormal FC between anterior cingulate and AI covaried with reduced glutamate level within cingulate cortex. Recently, deficient glial glutamate conversion was found in AI in major depression disorder (MDD). We therefore postulate a local glutamatergic mechanism in insula cortex of depressive patients, which is correlated with symptoms severity and itself influences AI's network connectivity in MDD. Twenty-five MDD patients and 25 healthy controls (HC) matched on age and sex underwent resting state functional magnetic resonance imaging and magnetic resonance spectroscopy scans. To determine the role of local glutamate-glutamine complex (Glx) ratio on whole brain AI FC, we conducted regression analysis with Glx relative to creatine (Cr) ratio as factor of interest and age, sex, and voxel tissue composition as nuisance factors. We found that in MDD, but not in HC, AI Glx/Cr ratio correlated positively with AI FC to right supramarginal gyrus and negatively with AI FC toward left occipital cortex (p < 0.05 family wise error). AI Glx/Cr level was negatively correlated with HAMD score (p < 0.05) in MDD patients. We showed that the local AI ratio of glutamatergic-creatine metabolism is an underlying candidate subserving functional network disintegration of insula toward low level and supramodal integration areas, in MDD. While causality cannot directly be inferred from such correlation, our finding helps to define a multilevel network of response-predicting regions based on local metabolism and connectivity strength.

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction

PubMed Central

Konova, Anna B.; Moeller, Scott J.; Tomasi, Dardo; Parvaz, Muhammad A.; Alia-Klein, Nelly; Volkow, Nora D.; Goldstein, Rita Z.

2012-01-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) which was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. PMID:22775285

Baseline Prevalence of Birth Defects Associated with Congenital Zika Virus Infection - Massachusetts, North Carolina, and Atlanta, Georgia, 2013-2014.

PubMed

Cragan, Janet D; Mai, Cara T; Petersen, Emily E; Liberman, Rebecca F; Forestieri, Nina E; Stevens, Alissa C; Delaney, Augustina; Dawson, April L; Ellington, Sascha R; Shapiro-Mendoza, Carrie K; Dunn, Julie E; Higgins, Cathleen A; Meyer, Robert E; Williams, Tonya; Polen, Kara N D; Newsome, Kim; Reynolds, Megan; Isenburg, Jennifer; Gilboa, Suzanne M; Meaney-Delman, Dana M; Moore, Cynthia A; Boyle, Coleen A; Honein, Margaret A

2017-03-03

Zika virus infection during pregnancy can cause serious brain abnormalities, but the full range of adverse outcomes is unknown (1). To better understand the impact of birth defects resulting from Zika virus infection, the CDC surveillance case definition established in 2016 for birth defects potentially related to Zika virus infection* (2) was retrospectively applied to population-based birth defects surveillance data collected during 2013-2014 in three areas before the introduction of Zika virus (the pre-Zika years) into the World Health Organization's Region of the Americas (Americas) (3). These data, from Massachusetts (2013), North Carolina (2013), and Atlanta, Georgia (2013-2014), included 747 infants and fetuses with one or more of the birth defects meeting the case definition (pre-Zika prevalence = 2.86 per 1,000 live births). Brain abnormalities or microcephaly were the most frequently recorded (1.50 per 1,000), followed by neural tube defects and other early brain malformations † (0.88), eye abnormalities without mention of a brain abnormality (0.31), and other consequences of central nervous system (CNS) dysfunction without mention of brain or eye abnormalities (0.17). During January 15-September 22, 2016, the U.S. Zika Pregnancy Registry (USZPR) reported 26 infants and fetuses with these same defects among 442 completed pregnancies (58.8 per 1,000) born to mothers with laboratory evidence of possible Zika virus infection during pregnancy (2). Although the ascertainment methods differed, this finding was approximately 20 times higher than the proportion of one or more of the same birth defects among pregnancies during the pre-Zika years. These data demonstrate the importance of population-based surveillance for interpreting data about birth defects potentially related to Zika virus infection.

Brain growth across the life span in autism: age-specific changes in anatomical pathology.

PubMed

Courchesne, Eric; Campbell, Kathleen; Solso, Stephanie

2011-03-22

Autism is marked by overgrowth of the brain at the earliest ages but not at older ages when decreases in structural volumes and neuron numbers are observed instead. This has led to the theory of age-specific anatomic abnormalities in autism. Here we report age-related changes in brain size in autistic and typical subjects from 12 months to 50 years of age based on analyses of 586 longitudinal and cross-sectional MRI scans. This dataset is several times larger than the largest autism study to date. Results demonstrate early brain overgrowth during infancy and the toddler years in autistic boys and girls, followed by an accelerated rate of decline in size and perhaps degeneration from adolescence to late middle age in this disorder. We theorize that underlying these age-specific changes in anatomic abnormalities in autism, there may also be age-specific changes in gene expression, molecular, synaptic, cellular, and circuit abnormalities. A peak age for detecting and studying the earliest fundamental biological underpinnings of autism is prenatal life and the first three postnatal years. Studies of the older autistic brain may not address original causes but are essential to discovering how best to help the older aging autistic person. Lastly, the theory of age-specific anatomic abnormalities in autism has broad implications for a wide range of work on the disorder including the design, validation, and interpretation of animal model, lymphocyte gene expression, brain gene expression, and genotype/CNV-anatomic phenotype studies. Copyright © 2010 Elsevier B.V. All rights reserved.

Estimating intracranial volume using intracranial area in healthy children and those with childhood status epilepticus

PubMed Central

Piper, Rory J; Yoong, Michael M; Pujar, Suresh; Chin, Richard F

2014-01-01

Background Correcting volumetric measurements of brain structures for intracranial volume (ICV) is important in comparing volumes across subjects with different ICV. The aim of this study was to investigate whether intracranial area (ICA) reliably predicts actual ICV in a healthy pediatric cohort and in children with convulsive status epilepticus (CSE). Methods T1-weighted volumetric MRI was performed on 20 healthy children (control group), 10 with CSE with structurally normal MRI (CSE/MR-), and 12 with CSE with structurally abnormal MRI (CSE/MR+). ICA, using a mid-sagittal slice, and the actual ICV were measured. Results A high Spearman correlation was found between the ICA and ICV measurements in the control (r = 0.96; P < 0.0001), CSE/MR− (r = 0.93; P = 0.0003), and CSE/MR+ (r = 0.94; P < 0.0001) groups. On comparison of predicted and actual ICV, there was no significant difference in the CSE/MR− group (P = 0.77). However, the comparison between predicted and actual ICV was significantly different in the CSE/MR+ (P = 0.001) group. Our Bland–Altman plot showed that the ICA method consistently overestimated ICV in children in the CSE/MR+ group, especially in those with small ICV or widespread structural abnormalities. Conclusions After further validation, ICA measurement may be a reliable alternative to measuring actual ICV when correcting volume measurements for ICV, even in children with localized MRI abnormalities. Caution should be applied when the method is used in children with small ICV and those with multilobar brain pathology. PMID:25365798

Cortical Abnormalities Associated With Pediatric and Adult Obsessive-Compulsive Disorder: Findings From the ENIGMA Obsessive-Compulsive Disorder Working Group.

PubMed

Boedhoe, Premika S W; Schmaal, Lianne; Abe, Yoshinari; Alonso, Pino; Ameis, Stephanie H; Anticevic, Alan; Arnold, Paul D; Batistuzzo, Marcelo C; Benedetti, Francesco; Beucke, Jan C; Bollettini, Irene; Bose, Anushree; Brem, Silvia; Calvo, Anna; Calvo, Rosa; Cheng, Yuqi; Cho, Kang Ik K; Ciullo, Valentina; Dallaspezia, Sara; Denys, Damiaan; Feusner, Jamie D; Fitzgerald, Kate D; Fouche, Jean-Paul; Fridgeirsson, Egill A; Gruner, Patricia; Hanna, Gregory L; Hibar, Derrek P; Hoexter, Marcelo Q; Hu, Hao; Huyser, Chaim; Jahanshad, Neda; James, Anthony; Kathmann, Norbert; Kaufmann, Christian; Koch, Kathrin; Kwon, Jun Soo; Lazaro, Luisa; Lochner, Christine; Marsh, Rachel; Martínez-Zalacaín, Ignacio; Mataix-Cols, David; Menchón, José M; Minuzzi, Luciano; Morer, Astrid; Nakamae, Takashi; Nakao, Tomohiro; Narayanaswamy, Janardhanan C; Nishida, Seiji; Nurmi, Erika; O'Neill, Joseph; Piacentini, John; Piras, Fabrizio; Piras, Federica; Reddy, Y C Janardhan; Reess, Tim J; Sakai, Yuki; Sato, Joao R; Simpson, H Blair; Soreni, Noam; Soriano-Mas, Carles; Spalletta, Gianfranco; Stevens, Michael C; Szeszko, Philip R; Tolin, David F; van Wingen, Guido A; Venkatasubramanian, Ganesan; Walitza, Susanne; Wang, Zhen; Yun, Je-Yeon; Thompson, Paul M; Stein, Dan J; van den Heuvel, Odile A

2018-05-01

Brain imaging studies of structural abnormalities in OCD have yielded inconsistent results, partly because of limited statistical power, clinical heterogeneity, and methodological differences. The authors conducted meta- and mega-analyses comprising the largest study of cortical morphometry in OCD ever undertaken. T 1 -weighted MRI scans of 1,905 OCD patients and 1,760 healthy controls from 27 sites worldwide were processed locally using FreeSurfer to assess cortical thickness and surface area. Effect sizes for differences between patients and controls, and associations with clinical characteristics, were calculated using linear regression models controlling for age, sex, site, and intracranial volume. In adult OCD patients versus controls, we found a significantly lower surface area for the transverse temporal cortex and a thinner inferior parietal cortex. Medicated adult OCD patients also showed thinner cortices throughout the brain. In pediatric OCD patients compared with controls, we found significantly thinner inferior and superior parietal cortices, but none of the regions analyzed showed significant differences in surface area. However, medicated pediatric OCD patients had lower surface area in frontal regions. Cohen's d effect sizes varied from -0.10 to -0.33. The parietal cortex was consistently implicated in both adults and children with OCD. More widespread cortical thickness abnormalities were found in medicated adult OCD patients, and more pronounced surface area deficits (mainly in frontal regions) were found in medicated pediatric OCD patients. These cortical measures represent distinct morphological features and may be differentially affected during different stages of development and illness, and possibly moderated by disease profile and medication.

Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum.

PubMed

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S; Kiehl, Kent A; Koenigs, Michael

2017-03-01

Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates ( N =124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked.

Impulsive-antisocial dimension of psychopathy linked to enlargement and abnormal functional connectivity of the striatum

PubMed Central

Korponay, Cole; Pujara, Maia; Deming, Philip; Philippi, Carissa; Decety, Jean; Kosson, David S.; Kiehl, Kent A.; Koenigs, Michael

2016-01-01

Background Psychopathy is a mental health disorder characterized by callous and impulsive antisocial behavior, and is associated with a high incidence of violent crime, substance abuse, and recidivism. Recent studies suggest that the striatum may be a key component of the neurobiological basis for the disorder, though structural findings have been mixed and functional connectivity of the striatum in psychopathy has yet to be fully examined. Methods We performed a multimodal neuroimaging study of striatum volume and functional connectivity in psychopathy, using a large sample of adult male prison inmates (N=124). We conducted volumetric analyses in striatal subnuclei, and subsequently assessed resting-state functional connectivity in areas where volume was related to psychopathy severity. Results Total PCL-R and Factor 2 scores (which index the impulsive/antisocial traits of psychopathy) were associated with larger striatal subnuclei volumes and increased volume in focal areas throughout the striatum, particularly in the nucleus accumbens and putamen bilaterally. Furthermore, at many of the striatal areas where volume was positively associated with Factor 2 scores, psychopathy severity was also associated with abnormal functional connectivity with other brain regions, including dorsolateral prefrontal cortex, ventral midbrain and other areas of the striatum. The results were not attributable to age, race, IQ, substance use history, or intracranial volume. Conclusion These findings associate the impulsive/antisocial dimension of psychopathy with enlarged striatal subnuclei and aberrant functional connectivity between the striatum and other brain regions. Furthermore, the co-localization of volumetric and functional connectivity findings suggests that these neural abnormalities may be pathophysiologically linked. PMID:28367514

Alterations in White Matter Integrity in Young Adults with Smartphone Dependence

PubMed Central

Hu, Yuanming; Long, Xiaojing; Lyu, Hanqing; Zhou, Yangyang; Chen, Jianxiang

2017-01-01

Smartphone dependence (SPD) is increasingly regarded as a psychological problem, however, the underlying neural substrates of SPD is still not clear. High resolution magnetic resonance imaging provides a useful tool to help understand and manage the disorder. In this study, a tract-based spatial statistics (TBSS) analysis on diffusion tensor imaging (DTI) was used to measure white matter integrity in young adults with SPD. A total of 49 subjects were recruited and categorized into SPD and control group based on their clinical behavioral tests. To localize regions with abnormal white matter integrity in SPD, the voxel-wise analysis of fractional anisotropy (FA) and mean diffusivity (MD) on the whole brain was performed by TBSS. The correlation between the quantitative variables of brain structures and the behavior measures were performed. Our result demonstrated that SPD had significantly lower white matter integrity than controls in superior longitudinal fasciculus (SLF), superior corona radiata (SCR), internal capsule, external capsule, sagittal stratum, fornix/stria terminalis and midbrain structures. Correlation analysis showed that the observed abnormalities in internal capsule and stria terminalis were correlated with the severity of dependence and behavioral assessments. Our finding facilitated a primary understanding of white matter characteristics in SPD and indicated that the structural deficits might link to behavioral impairments. PMID:29163108

Abnormal high-energy phosphate molecule metabolism during regional brain activation in patients with bipolar disorder.

PubMed

Yuksel, C; Du, F; Ravichandran, C; Goldbach, J R; Thida, T; Lin, P; Dora, B; Gelda, J; O'Connor, L; Sehovic, S; Gruber, S; Ongur, D; Cohen, B M

2015-09-01

Converging evidence suggests bioenergetic abnormalities in bipolar disorder (BD). In the brain, phosphocreatine (PCr) acts a reservoir of high-energy phosphate (HEP) bonds, and creatine kinases (CK) catalyze the transfer of HEP from adenosine triphosphate (ATP) to PCr and from PCr back to ATP, at times of increased need. This study examined the activity of this mechanism in BD by measuring the levels of HEP molecules during a stimulus paradigm that increased local energy demand. Twenty-three patients diagnosed with BD-I and 22 healthy controls (HC) were included. Levels of phosphorus metabolites were measured at baseline and during visual stimulation in the occipital lobe using (31)P magnetic resonance spectroscopy at 4T. Changes in metabolite levels showed different patterns between the groups. During stimulation, HC had significant reductions in PCr but not in ATP, as expected. In contrast, BD patients had significant reductions in ATP but not in PCr. In addition, PCr/ATP ratio was lower at baseline in patients, and there was a higher change in this measure during stimulation. This pattern suggests a disease-related failure to replenish ATP from PCr through CK enzyme catalysis during tissue activation. Further studies measuring the CK flux in BD are required to confirm and extend this finding.

Paired Helical Filaments from Alzheimer Disease Brain Induce Intracellular Accumulation of Tau Protein in Aggresomes*

PubMed Central

Santa-Maria, Ismael; Varghese, Merina; Ksiȩżak-Reding, Hanna; Dzhun, Anastasiya; Wang, Jun; Pasinetti, Giulio M.

2012-01-01

Abnormal folding of tau protein leads to the generation of paired helical filaments (PHFs) and neurofibrillary tangles, a key neuropathological feature in Alzheimer disease and tauopathies. A specific anatomical pattern of pathological changes developing in the brain suggests that once tau pathology is initiated it propagates between neighboring neuronal cells, possibly spreading along the axonal network. We studied whether PHFs released from degenerating neurons could be taken up by surrounding cells and promote spreading of tau pathology. Neuronal and non-neuronal cells overexpressing green fluorescent protein-tagged tau (GFP-Tau) were treated with isolated fractions of human Alzheimer disease-derived PHFs for 24 h. We found that cells internalized PHFs through an endocytic mechanism and developed intracellular GFP-Tau aggregates with attributes of aggresomes. This was particularly evident by the perinuclear localization of aggregates and redistribution of the vimentin intermediate filament network and retrograde motor protein dynein. Furthermore, the content of Sarkosyl-insoluble tau, a measure of abnormal tau aggregation, increased 3-fold in PHF-treated cells. An exosome-related mechanism did not appear to be involved in the release of GFP-Tau from untreated cells. The evidence that cells can internalize PHFs, leading to formation of aggresome-like bodies, opens new therapeutic avenues to prevent propagation and spreading of tau pathology. PMID:22496370

Epilepsy

MedlinePlus

... made great strides in detecting patterns of abnormal electrical activity in the brain that cause epileptic seizures. A technology to measure brain activity, called electroencephalography (EEG), became ...

Man Versus Machine Part 2: Comparison of Radiologists' Interpretations and NeuroQuant Measures of Brain Asymmetry and Progressive Atrophy in Patients With Traumatic Brain Injury.

PubMed

Ross, David E; Ochs, Alfred L; DeSmit, Megan E; Seabaugh, Jan M; Havranek, Michael D

2015-01-01

This study is an expanded version of an earlier study, which compared NeuroQuant measures of MRI brain volume with the radiologist's traditional approach in outpatients with mild or moderate traumatic brain injury. NeuroQuant volumetric analyses were compared with the radiologists' interpretations. NeuroQuant found significantly higher rates of atrophy (50.0%), abnormal asymmetry (83.3%), and progressive atrophy (70.0%) than the radiologists (12.5%, 0% and 0%, respectively). Overall, NeuroQuant was more sensitive for detecting at least one sign of atrophy, abnormal asymmetry, or progressive atrophy (95.8%) than the traditional radiologist's approach (12.5%).

Genetics Home Reference: megalencephaly-polymicrogyria-polydactyly-hydrocephalus syndrome

MedlinePlus

... with a brain abnormality called bilateral perisylvian polymicrogyria (BPP). The surface of the brain normally has many ridges or folds, called gyri. In people with BPP, an area of the brain called the perisylvian ...

The Chronic Encephalopathy of Parry Romberg Syndrome and En Coupe De Sabre with a 31-Year-History in a West Indian Woman: Clinical, Immunologic and Neuroimaging Abnormalities.

PubMed

Seegobin, Karan; Abdool, Kamille; Ramcharan, Kanterpersad; Dyaanand, Haramnauth; Rampersad, Fidel

2016-09-30

We describe a case of Parry Romberg syndrome/ en coupe de sabre in a woman whose disease started as seizures at age 8 but was diagnosed at the age 39. During these 31 years she got married, completed a first degree at university, had two successful pregnancies and has been gainfully employed. The features of generalized tonic-clonic seizures, autoimmune abnormalities, ocular abnormalities, morphea en coup de sabre and brain imaging abnormalities were present. Areas of parietal lobe cerebral calcification were encountered on the computed tomographic scan and bilateral periventricular white matter changes on the magnetic resonance imaging with frontal, temporal and parietal lobe brain atrophy ipsilateral to the facial hemiatrophy. Clinical, immunologic and neuroradiological abnormalities are discussed. In some cases, this illness can run a benign and stable course.

Measurement of cerebral perfusion after zolpidem administration in the baboon model.

PubMed

Clauss, R P; Dormehl, I C; Oliver, D W; Nel, W H; Kilian, E; Louw, W K

2001-01-01

A recent report showed that zolpidem (CAS 82626-48-0) can lead to the arousal of a semi-comatosed patient. Zolpidem is clinically used for the treatment of insomnia. It belongs to the imidazopyridine chemical class and is a non benzodiazepine drug. It illicits its pharmacological action via the GABA receptor system through stimulation of particularly the omega 1 receptors. In this study, the effect of zolpidem on brain perfusion was examined by 99mTc hexamethyl-propylene amine oxime (HMPAO) split dose brain SPECT on four normal baboons and in one baboon with abnormal neurological behaviour. The global and regional brain perfusion was not significantly affected in the normal brains. In some regions of the abnormal baboon brain, however, there was a disproportionate increase in perfusion after zolpidem.

Large-scale brain networks are distinctly affected in right and left mesial temporal lobe epilepsy.

PubMed

de Campos, Brunno Machado; Coan, Ana Carolina; Lin Yasuda, Clarissa; Casseb, Raphael Fernandes; Cendes, Fernando

2016-09-01

Mesial temporal lobe epilepsy (MTLE) with hippocampus sclerosis (HS) is associated with functional and structural alterations extending beyond the temporal regions and abnormal pattern of brain resting state networks (RSNs) connectivity. We hypothesized that the interaction of large-scale RSNs is differently affected in patients with right- and left-MTLE with HS compared to controls. We aimed to determine and characterize these alterations through the analysis of 12 RSNs, functionally parceled in 70 regions of interest (ROIs), from resting-state functional-MRIs of 99 subjects (52 controls, 26 right- and 21 left-MTLE patients with HS). Image preprocessing and statistical analysis were performed using UF(2) C-toolbox, which provided ROI-wise results for intranetwork and internetwork connectivity. Intranetwork abnormalities were observed in the dorsal default mode network (DMN) in both groups of patients and in the posterior salience network in right-MTLE. Both groups showed abnormal correlation between the dorsal-DMN and the posterior salience, as well as between the dorsal-DMN and the executive-control network. Patients with left-MTLE also showed reduced correlation between the dorsal-DMN and visuospatial network and increased correlation between bilateral thalamus and the posterior salience network. The ipsilateral hippocampus stood out as a central area of abnormalities. Alterations on left-MTLE expressed a low cluster coefficient, whereas the altered connections on right-MTLE showed low cluster coefficient in the DMN but high in the posterior salience regions. Both right- and left-MTLE patients with HS have widespread abnormal interactions of large-scale brain networks; however, all parameters evaluated indicate that left-MTLE has a more intricate bihemispheric dysfunction compared to right-MTLE. Hum Brain Mapp 37:3137-3152, 2016. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc. © 2016 The Authors Human Brain Mapping Published by Wiley Periodicals, Inc.

Neuroimaging parameters in early open spina bifida detection. Further benefit in first trimester screening?

PubMed

Iliescu, D; Comănescu, A; Antsaklis, P; Tudorache, Stefania; Ghiluşi, Mirela; Comănescu, Violeta; Paulescu, Daniela; Ceauşu, Iuliana; Antsaklis, A; Novac, Liliana; Cernea, N

2011-01-01

Morphological investigation of the central nervous system (CNS) in fetuses with positive markers for open spina bifida (OSB) detection, visualized by ultrasound during the first trimester of pregnancy. Data from fetuses that underwent routine first trimester ultrasound scan in our center during September 2007-March 2011 and presented abnormal aspects of the fourth ventricle, also referred as intracranial translucency (IT), provided the morphological support to evaluate CNS features. A neuro-histological study of posterior cerebral fossa illustrated anatomical features of the structures involved in the sonographic first trimester detection of neural tube defects. Abnormal IT aspects were found in OSB cases examined in the first trimester, but also in other severe cerebral abnormalities. Brain stem antero-posterior diameter (BS) and brain stem to occipital bone (BSOB) ratio may be more specific for OSB detection. Correlations between histological aspects of posterior brain fossa and ultrasound standard assessment have been made; highlighting the anatomical features involved by the new techniques developed for OSB early detection. Preliminary results show that modern sonographic protocols are capable to detect abnormalities in the morphometry of the posterior brain. First trimester fourth ventricle abnormalities should be followed by careful CNS evaluation because are likely to appear in OSB affected fetuses, but also in other CNS severe anomalies; in such cases, normal BS and BSOB ratio may serve as indirect argument for spine integrity, if specificity is confirmed in large series of fetuses.

Integrative assessment of brain function in PTSD: brain stability and working memory.

PubMed

Veltmeyer, Melinda D; McFarlane, Alexander C; Bryant, Richard A; Mayo, Therese; Gordon, Evian; Clark, C Richard

2006-03-01

Posttraumatic Stress Disorder (PTSD) is characterized by symptoms of hyperarousal, avoidance and intrusive trauma-related memories and deficits in everyday memory and attention. Separate studies in PTSD have found abnormalities in electroencephalogram EEG, in event-related potential (ERP) and behavioral measures of working memory and attention. The present study seeks to determine whether these abnormalities are related and the extent to which they share this relationship with clinical symptoms. EEG data were collected during an eyes-open paradigm and a one-back working memory task. Behavioral and clinical data (CAPS) were also collected. The PTSD group showed signs of altered cortical arousal as indexed by reduced alpha power and an increased theta/alpha ratio, and clinical and physiological measures of arousal were found to be related. The normal relationship between theta power and ERP indices of working memory was not affected in PTSD, with both sets of measures reduced in the disordered group. Medication appeared to underpin a number of abnormal parameters, including P3 amplitude to targets and the accuracy, though not speed, of target detection. The present study helps to overcome a limitation of earlier studies that assess such parameters independently in different groups of patients that vary in factors such as comorbidity, medication status, gender and symptom profile. The present study begins to shed light on the relationship between these measures and suggests that abnormalities in brain working memory may be linked to underlying abnormalities in brain stability.

Large national series of patients with Xq28 duplication involving MECP2: Delineation of brain MRI abnormalities in 30 affected patients.

PubMed

El Chehadeh, Salima; Faivre, Laurence; Mosca-Boidron, Anne-Laure; Malan, Valérie; Amiel, Jeanne; Nizon, Mathilde; Touraine, Renaud; Prieur, Fabienne; Pasquier, Laurent; Callier, Patrick; Lefebvre, Mathilde; Marle, Nathalie; Dubourg, Christèle; Julia, Sophie; Sarret, Catherine; Francannet, Christine; Laffargue, Fanny; Boespflug-Tanguy, Odile; David, Albert; Isidor, Bertrand; Le Caignec, Cédric; Vigneron, Jacqueline; Leheup, Bruno; Lambert, Laetitia; Philippe, Christophe; Cuisset, Jean-Marie; Andrieux, Joris; Plessis, Ghislaine; Toutain, Annick; Goldenberg, Alice; Cormier-Daire, Valérie; Rio, Marlène; Bonnefont, Jean-Paul; Thevenon, Julien; Echenne, Bernard; Journel, Hubert; Afenjar, Alexandra; Burglen, Lydie; Bienvenu, Thierry; Addor, Marie-Claude; Lebon, Sébastien; Martinet, Danièle; Baumann, Clarisse; Perrin, Laurence; Drunat, Séverine; Jouk, Pierre-Simon; Devillard, Françoise; Coutton, Charles; Lacombe, Didier; Delrue, Marie-Ange; Philip, Nicole; Moncla, Anne; Badens, Catherine; Perreton, Nathalie; Masurel, Alice; Thauvin-Robinet, Christel; Des Portes, Vincent; Guibaud, Laurent

2016-01-01

Xq28 duplications encompassing MECP2 have been described in male patients with a severe neurodevelopmental disorder associated with hypotonia and spasticity, severe learning disability, stereotyped movements, and recurrent pulmonary infections. We report on standardized brain magnetic resonance imaging (MRI) data of 30 affected patients carrying an Xq28 duplication involving MECP2 of various sizes (228 kb to 11.7 Mb). The aim of this study was to seek recurrent malformations and attempt to determine whether variations in imaging features could be explained by differences in the size of the duplications. We showed that 93% of patients had brain MRI abnormalities such as corpus callosum abnormalities (n = 20), reduced volume of the white matter (WM) (n = 12), ventricular dilatation (n = 9), abnormal increased hyperintensities on T2-weighted images involving posterior periventricular WM (n = 6), and vermis hypoplasia (n = 5). The occipitofrontal circumference varied considerably between >+2SD in five patients and <-2SD in four patients. Among the nine patients with dilatation of the lateral ventricles, six had a duplication involving L1CAM. The only patient harboring bilateral posterior subependymal nodular heterotopia also carried an FLNA gene duplication. We could not demonstrate a correlation between periventricular WM hyperintensities/delayed myelination and duplication of the IKBKG gene. We thus conclude that patients with an Xq28 duplication involving MECP2 share some similar but non-specific brain abnormalities. These imaging features, therefore, could not constitute a diagnostic clue. The genotype-phenotype correlation failed to demonstrate a relationship between the presence of nodular heterotopia, ventricular dilatation, WM abnormalities, and the presence of FLNA, L1CAM, or IKBKG, respectively, in the duplicated segment. © 2015 Wiley Periodicals, Inc.

The role of biomarkers and MEG-based imaging markers in the diagnosis of post-traumatic stress disorder and blast-induced mild traumatic brain injury.

PubMed

Huang, Mingxiong; Risling, Mårten; Baker, Dewleen G

2016-01-01

Pervasive use of improvised explosive devices (IEDs), rocket-propelled grenades, and land mines in the recent conflicts in Iraq and Afghanistan has brought traumatic brain injury (TBI) and its impact on health outcomes into public awareness. Blast injuries have been deemed signature wounds of these wars. War-related TBI is not new, having become prevalent during WWI and remaining medically relevant in WWII and beyond. Medicine's past attempts to accurately diagnose and disentangle the pathophysiology of war-related TBI parallels current lines of inquiry and highlights limitations in methodology and attribution of symptom etiology, be it organic, psychological, or behavioral. New approaches and biomarkers are needed. Serological biomarkers and biomarkers of injury obtained with imaging techniques represent cornerstones in the translation between experimental data and clinical observations. Experimental models for blast related TBI and PTSD can generate critical data on injury threshold, for example for white matter injury from acceleration. Carefully verified and validated models can be evaluated with gene expression arrays and proteomics to identify new candidates for serological biomarkers. Such models can also be analyzed with diffusion MRI and microscopy in order to identify criteria for detection of diffuse white matter injuries, such as DAI (diffuse axonal injury). The experimental models can also be analyzed with focus on injury outcome in brain stem regions, such as locus coeruleus or nucleus raphe magnus that can be involved in response to anxiety changes. Mild (and some moderate) TBI can be difficult to diagnose because the injuries are often not detectable on conventional MRI or CT. There is accumulating evidence that injured brain tissues in TBI patients generate abnormal low-frequency magnetic activity (ALFMA, peaked at 1-4Hz) that can be measured and localized by magnetoencephalography (MEG). MEG imaging detects TBI abnormalities at the rates of 87% for the mild TBI, group (blast-induced plus non-blast causes) and 100% for the moderate group. Among the mild TBI patients, the rates of abnormalities are 96% and 77% for the blast and non-blast TBI groups, respectively. There is emerging evidence based on fMRI and MEG studies showing hyper-activity in the amygdala and hypo-activity in pre-frontal cortex in individuals with PTSD. MEG signal may serve as a sensitive imaging marker for mTBI, distinguishable from abnormalities generated in association with PTSD. More work is needed to fully describe physiological mechanisms of post-concussive symptoms. Published by Elsevier Ltd.

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS.

PubMed

Silva, Mauro Sb; Prescott, Melanie; Campbell, Rebecca E

2018-04-05

Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP-transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype.

Ontogeny and reversal of brain circuit abnormalities in a preclinical model of PCOS

PubMed Central

Silva, Mauro S.B.; Prescott, Melanie; Campbell, Rebecca E.

2018-01-01

Androgen excess is a hallmark of polycystic ovary syndrome (PCOS), a prevalent yet poorly understood endocrine disorder. Evidence from women and preclinical animal models suggests that elevated perinatal androgens can elicit PCOS onset in adulthood, implying androgen actions in both PCOS ontogeny and adult pathophysiology. Prenatally androgenized (PNA) mice exhibit a robust increase of progesterone-sensitive GABAergic inputs to gonadotropin-releasing hormone (GnRH) neurons implicated in the pathogenesis of PCOS. It is unclear when altered GABAergic wiring develops in the brain, and whether these central abnormalities are dependent upon adult androgen excess. Using GnRH-GFP–transgenic mice, we determined that increased GABA input to GnRH neurons occurs prior to androgen excess and the manifestation of reproductive impairments in PNA mice. These data suggest that brain circuit abnormalities precede the postpubertal development of PCOS traits. Despite the apparent developmental programming of circuit abnormalities, long-term blockade of androgen receptor signaling from early adulthood rescued normal GABAergic wiring onto GnRH neurons, improved ovarian morphology, and restored reproductive cycles in PNA mice. Therefore, androgen excess maintains changes in female brain wiring linked to PCOS features and the blockade of androgen receptor signaling reverses both the central and peripheral PNA-induced PCOS phenotype. PMID:29618656

mTOR regulates brain morphogenesis by mediating GSK3 signaling

PubMed Central

Ka, Minhan; Condorelli, Gianluigi; Woodgett, James R.; Kim, Woo-Yang

2014-01-01

Balanced control of neural progenitor maintenance and neuron production is crucial in establishing functional neural circuits during brain development, and abnormalities in this process are implicated in many neurological diseases. However, the regulatory mechanisms of neural progenitor homeostasis remain poorly understood. Here, we show that mammalian target of rapamycin (mTOR) is required for maintaining neural progenitor pools and plays a key role in mediating glycogen synthase kinase 3 (GSK3) signaling during brain development. First, we generated and characterized conditional mutant mice exhibiting deletion of mTOR in neural progenitors and neurons in the developing brain using Nestin-cre and Nex-cre lines, respectively. The elimination of mTOR resulted in abnormal cell cycle progression of neural progenitors in the developing brain and thereby disruption of progenitor self-renewal. Accordingly, production of intermediate progenitors and postmitotic neurons were markedly suppressed. Next, we discovered that GSK3, a master regulator of neural progenitors, interacts with mTOR and controls its activity in cortical progenitors. Finally, we found that inactivation of mTOR activity suppresses the abnormal proliferation of neural progenitors induced by GSK3 deletion. Our findings reveal that the interaction between mTOR and GSK3 signaling plays an essential role in dynamic homeostasis of neural progenitors during brain development. PMID:25273085

Resting state fMRI entropy probes complexity of brain activity in adults with ADHD.

PubMed

Sokunbi, Moses O; Fung, Wilson; Sawlani, Vijay; Choppin, Sabine; Linden, David E J; Thome, Johannes

2013-12-30

In patients with attention deficit hyperactivity disorder (ADHD), quantitative neuroimaging techniques have revealed abnormalities in various brain regions, including the frontal cortex, striatum, cerebellum, and occipital cortex. Nonlinear signal processing techniques such as sample entropy have been used to probe the regularity of brain magnetoencephalography signals in patients with ADHD. In the present study, we extend this technique to analyse the complex output patterns of the 4 dimensional resting state functional magnetic resonance imaging signals in adult patients with ADHD. After adjusting for the effect of age, we found whole brain entropy differences (P=0.002) between groups and negative correlation (r=-0.45) between symptom scores and mean whole brain entropy values, indicating lower complexity in patients. In the regional analysis, patients showed reduced entropy in frontal and occipital regions bilaterally and a significant negative correlation between the symptom scores and the entropy maps at a family-wise error corrected cluster level of P<0.05 (P=0.001, initial threshold). Our findings support the hypothesis of abnormal frontal-striatal-cerebellar circuits in ADHD and the suggestion that sample entropy is a useful tool in revealing abnormalities in the brain dynamics of patients with psychiatric disorders. © 2013 Elsevier Ireland Ltd. All rights reserved.

Disrupted Cerebro-cerebellar Intrinsic Functional Connectivity in Young Adults with High-functioning Autism Spectrum Disorder: A Data-driven, Whole-brain, High Temporal Resolution fMRI Study.

PubMed

Arnold Anteraper, Sheeba; Guell, Xavier; D'Mello, Anila; Joshi, Neha; Whitfield-Gabrieli, Susan; Joshi, Gagan

2018-06-13

To examine the resting-state functional-connectivity (RsFc) in young adults with high-functioning autism spectrum disorder (HF-ASD) using state-of-the-art fMRI data acquisition and analysis techniques. Simultaneous multi-slice, high temporal resolution fMRI acquisition; unbiased whole-brain connectome-wide multivariate pattern analysis (MVPA) techniques for assessing RsFc; and post-hoc whole-brain seed-to-voxel analyses using MVPA results as seeds. MVPA revealed two clusters of abnormal connectivity in the cerebellum. Whole-brain seed-based functional connectivity analyses informed by MVPA-derived clusters showed significant under connectivity between the cerebellum and social, emotional, and language brain regions in the HF-ASD group compared to healthy controls. The results we report are coherent with existing structural, functional, and RsFc literature in autism, extend previous literature reporting cerebellar abnormalities in the neuropathology of autism, and highlight the cerebellum as a potential target for therapeutic, diagnostic, predictive, and prognostic developments in ASD. The description of functional connectivity abnormalities using whole-brain, data-driven analyses as reported in the present study may crucially advance the development of ASD biomarkers, targets for therapeutic interventions, and neural predictors for measuring treatment response.

Decision-making deficit of a patient with axonal damage after traumatic brain injury.

PubMed

Yasuno, Fumihiko; Matsuoka, Kiwamu; Kitamura, Soichiro; Kiuchi, Kuniaki; Kosaka, Jun; Okada, Koji; Tanaka, Syohei; Shinkai, Takayuki; Taoka, Toshiaki; Kishimoto, Toshifumi

2014-02-01

Patients with traumatic brain injury (TBI) were reported to have difficulty making advantageous decisions, but the underlying deficits of the network of brain areas involved in this process were not directly examined. We report a patient with TBI who demonstrated problematic behavior in situations of risk and complexity after cerebral injury from a traffic accident. The Iowa gambling task (IGT) was used to reveal his deficits in the decision-making process. To examine underlying deficits of the network of brain areas, we examined T1-weighted structural MRI, diffusion tensor imaging (DTI) and Tc-ECD SPECT in this patient. The patient showed abnormality in IGT. DTI-MRI results showed a significant decrease in fractional anisotropy (FA) in the fasciculus between the brain stem and cortical regions via the thalamus. He showed significant decrease in gray matter volumes in the bilateral insular cortex, hypothalamus, and posterior cingulate cortex, possibly reflecting Wallerian degeneration secondary to the fasciculus abnormalities. SPECT showed significant blood flow decrease in the broad cortical areas including the ventromedial prefrontal cortex (VM). Our study showed that the patient had dysfunctional decision-making process. Microstructural abnormality in the fasciculus, likely from the traffic accident, caused reduced afferent feedback to the brain, resulting in less efficient decision-making. Our findings support the somatic-marker hypothesis (SMH), where somatic feedback to the brain influences the decision-making process. Copyright © 2013 Elsevier Inc. All rights reserved.

Brain MRI and MR Spectroscopy Findings in Children with Nutritional Vitamin B12 Deficiency.

PubMed

Ekici, F; Tekbas, G; Hattapoğlu, S; Yaramış, A; Önder, H; Bilici, A

2016-06-01

Our aim in this study was to analyze the findings of brain magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) of children with vitamin B12 deficiency. This study included 14 cases. The findings of brain MRI and MRS in all cases were investigated. Four patients had been followed up and mean follow-up time 71.8 (59-85) day. Eight patients of the cases (57 %) had at least one abnormal MRI finding. The most commonly found MRI findings were thinning of the corpus callosum and brain atrophy, respectively. The mean ratio of NAA/Cr and Cho/Cr were measured in MRS, with values of 1.31 ± 0.17 and 1.04 ± 0.27, respectively. In two of three patients with abnormal MRI studies at presentation, subsequent MRI showed improvement while one patient remained unchanged. An increase in the ratios of metabolites were found in one case with control MRS. There was no lactate peak. Brain MRI was abnormal in more than half of the cases of children with vitamin B12 deficiency. Our radiologic findings similar with literature. There was no identifiable lactate peak. B12 deficiency could be the cause of the thinning of the corpus callosum and brain atrophy in the children that were given a brain MRI.

The maternal brain and its plasticity in humans

PubMed Central

Kim, Pilyoung; Strathearn, Lane; Swain, James E.

2015-01-01

Early mother-infant relationships play important roles in infants’ optimal development. New mothers undergo neurobiological changes that support developing mother-infant relationships regardless of great individual differences in those relationships. In this article, we review the neural plasticity in human mothers’ brains based on functional magnetic resonance imaging (fMRI) studies. First, we review the neural circuits that are involved in establishing and maintaining mother-infant relationships. Second, we discuss early postpartum factors (e.g., birth and feeding methods, hormones, and parental sensitivity) that are associated with individual differences in maternal brain neuroplasticity. Third, we discuss abnormal changes in the maternal brain related to psychopathology (i.e., postpartum depression, posttraumatic stress disorder, substance abuse) and potential brain remodeling associated with interventions. Last, we highlight potentially important future research directions to better understand normative changes in the maternal brain and risks for abnormal changes that may disrupt early mother-infant relationships. PMID:26268151

Pathogenesis of Hepatic Encephalopathy

PubMed Central

Ciećko-Michalska, Irena; Szczepanek, Małgorzata; Słowik, Agnieszka; Mach, Tomasz

2012-01-01

Hepatic encephalopathy can be a serious complication of acute liver failure and chronic liver diseases, predominantly liver cirrhosis. Hyperammonemia plays the most important role in the pathogenesis of hepatic encephalopathy. The brain-blood barrier disturbances, changes in neurotransmission, neuroinflammation, oxidative stress, GABA-ergic or benzodiazepine pathway abnormalities, manganese neurotoxicity, brain energetic disturbances, and brain blood flow abnormalities are considered to be involved in the development of hepatic encephalopathy. The influence of small intestine bacterial overgrowth (SIBO) on the induction of minimal hepatic encephalopathy is recently emphasized. The aim of this paper is to present the current views on the pathogenesis of hepatic encephalopathy. PMID:23316223

SPET brain perfusion imaging in mild traumatic brain injury without loss of consciousness and normal computed tomography.

PubMed

Abu-Judeh, H H; Parker, R; Singh, M; el-Zeftawy, H; Atay, S; Kumar, M; Naddaf, S; Aleksic, S; Abdel-Dayem, H M

1999-06-01

We present SPET brain perfusion findings in 32 patients who suffered mild traumatic brain injury without loss of consciousness and normal computed tomography. None of the patients had previous traumatic brain injury, CVA, HIV, psychiatric disorders or a history of alcohol or drug abuse. Their ages ranged from 11 to 61 years (mean = 42). The study was performed in 20 patients (62%) within 3 months of the date of injury and in 12 (38%) patients more than 3 months post-injury. Nineteen patients (60%) were involved in a motor vehicle accident, 10 patients (31%) sustained a fall and three patients (9%) received a blow to the head. The most common complaints were headaches in 26 patients (81%), memory deficits in 15 (47%), dizziness in 13 (41%) and sleep disorders in eight (25%). The studies were acquired approximately 2 h after an intravenous injection of 740 MBq (20.0 mCi) of 99Tcm-HMPAO. All images were acquired on a triple-headed gamma camera. The data were displayed on a 10-grade colour scale, with 2-pixel thickness (7.4 mm), and were reviewed blind to the patient's history of symptoms. The cerebellum was used as the reference site (100% maximum value). Any decrease in cerebral perfusion in the cortex or basal ganglia less than 70%, or less than 50% in the medial temporal lobe, compared to the cerebellar reference was considered abnormal. The results show that 13 (41%) had normal studies and 19 (59%) were abnormal (13 studies performed within 3 months of the date of injury and six studies performed more than 3 months post-injury). Analysis of the abnormal studies revealed that 17 showed 48 focal lesions and two showed diffuse supratentorial hypoperfusion (one from each of the early and delayed imaging groups). The 12 abnormal studies performed early had 37 focal lesions and averaged 3.1 lesions per patient, whereas there was a reduction to--an average of 2.2 lesions per patient in the five studies (total 11 lesions) performed more than 3 months post-injury. In the 17 abnormal studies with focal lesions, the following regions were involved in descending frequency: frontal lobes 58%, basal ganglia and thalami 47%, temporal lobes 26% and parietal lobes 16%. We conclude that: (1) SPET brain perfusion imaging is valuable and sensitive for the evaluation of cerebral perfusion changes following mild traumatic brain injury; (2) these changes can occur without loss of consciousness; (3) SPET brain perfusion imaging is more sensitive than computed tomography in detecting brain lesions; and (4) the changes may explain a neurological component of the patient's symptoms in the absence of morphological abnormalities using other imaging modalities.

Simultaneous and Noninvasive Imaging of Cerebral Oxygen Metabolic Rate, Blood Flow and Oxygen Extraction Fraction in Stroke Mice

PubMed Central

Zhu, Xiao-Hong; Chen, James; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2012-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO2) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO2 and CBF. This study employed the recently developed in vivo 17O MR spectroscopic imaging to simultaneously assess CMRO2, CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of 17O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive 17O-MR approach for rapidly imaging CMRO2, CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO2 and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising 17O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This 17O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. PMID:23000789

Simultaneous and noninvasive imaging of cerebral oxygen metabolic rate, blood flow and oxygen extraction fraction in stroke mice.

PubMed

Zhu, Xiao-Hong; Chen, James M; Tu, Tsang-Wei; Chen, Wei; Song, Sheng-Kwei

2013-01-01

Many brain diseases have been linked to abnormal oxygen metabolism and blood perfusion; nevertheless, there is still a lack of robust diagnostic tools for directly imaging cerebral metabolic rate of oxygen (CMRO(2)) and cerebral blood flow (CBF), as well as the oxygen extraction fraction (OEF) that reflects the balance between CMRO(2) and CBF. This study employed the recently developed in vivo (17)O MR spectroscopic imaging to simultaneously assess CMRO(2), CBF and OEF in the brain using a preclinical middle cerebral arterial occlusion mouse model with a brief inhalation of (17)O-labeled oxygen gas. The results demonstrated high sensitivity and reliability of the noninvasive (17)O-MR approach for rapidly imaging CMRO(2), CBF and OEF abnormalities in the ischemic cortex of the MCAO mouse brain. It was found that in the ischemic brain regions both CMRO(2) and CBF were substantially lower than that of intact brain regions, even for the mildly damaged brain regions that were unable to be clearly identified by the conventional MRI. In contrast, OEF was higher in the MCAO affected brain regions. This study demonstrates a promising (17)O MRI technique for imaging abnormal oxygen metabolism and perfusion in the diseased brain regions. This (17)O MRI technique is advantageous because of its robustness, simplicity, noninvasiveness and reliability: features that are essential to potentially translate it to human patients for early diagnosis and monitoring of treatment efficacy. Copyright © 2012 Elsevier Inc. All rights reserved.

Epilepsy in Adults with TSC

MedlinePlus

... are episodes of disturbed brain function that cause changes in attention or behavior. They are caused by abnormally excited electrical signals in the brain, like a lightning storm in the brain. Seizure types vary ... all seizures result from a sudden change in how the cells of the brain send ...

Description of 13 Infants Born During October 2015-January 2016 With Congenital Zika Virus Infection Without Microcephaly at Birth - Brazil.

PubMed

van der Linden, Vanessa; Pessoa, André; Dobyns, William; Barkovich, A James; Júnior, Hélio van der Linden; Filho, Epitacio Leite Rolim; Ribeiro, Erlane Marques; Leal, Mariana de Carvalho; Coimbra, Pablo Picasso de Araújo; Aragão, Maria de Fátima Viana Vasco; Verçosa, Islane; Ventura, Camila; Ramos, Regina Coeli; Cruz, Danielle Di Cavalcanti Sousa; Cordeiro, Marli Tenório; Mota, Vivian Maria Ribeiro; Dott, Mary; Hillard, Christina; Moore, Cynthia A

2016-12-02

Congenital Zika virus infection can cause microcephaly and severe brain abnormalities (1). Congenital Zika syndrome comprises a spectrum of clinical features (2); however, as is the case with most newly recognized teratogens, the earliest documented clinical presentation is expected to be the most severe. Initial descriptions of the effects of in utero Zika virus infection centered prominently on the finding of congenital microcephaly (3). To assess the possibility of clinical presentations that do not include congenital microcephaly, a retrospective assessment of 13 infants from the Brazilian states of Pernambuco and Ceará with normal head size at birth and laboratory evidence of congenital Zika virus infection was conducted. All infants had brain abnormalities on neuroimaging consistent with congenital Zika syndrome, including decreased brain volume, ventriculomegaly, subcortical calcifications, and cortical malformations. The earliest evaluation occurred on the second day of life. Among all infants, head growth was documented to have decelerated as early as 5 months of age, and 11 infants had microcephaly. These findings provide evidence that among infants with prenatal exposure to Zika virus, the absence of microcephaly at birth does not exclude congenital Zika virus infection or the presence of Zika-related brain and other abnormalities. These findings support the recommendation for comprehensive medical and developmental follow-up of infants exposed to Zika virus prenatally. Early neuroimaging might identify brain abnormalities related to congenital Zika infection even among infants with a normal head circumference (4).

Regional homogeneity associated with overgeneral autobiographical memory of first-episode treatment-naive patients with major depressive disorder in the orbitofrontal cortex: A resting-state fMRI study.

PubMed

Liu, Yansong; Zhao, Xudong; Cheng, Zaohuo; Zhang, Fuquan; Chang, Jun; Wang, Haosen; Xie, Rukui; Wang, Zhiqiang; Cao, Leiming; Wang, Guoqiang

2017-02-01

Overgeneral autobiographical memory (OGM) is involved in the onset and maintenance of depression. Recent studies have shown correlations between OGM and alterations of some brain regions by using task-state functional magnetic resonance imaging (fMRI). However, the correlation between OGM and spontaneous brain activity in depression remains unclear. The purpose of this study was to determine whether patients with major depressive disorder (MDD) show abnormal regional homogeneity (ReHo) and, if so, whether the brain areas with abnormal ReHo are associated with OGM. Twenty five patients with MDD and 25 age-matched, sex-matched, and education-matched healthy controls underwent resting-state fMRI. All participants were also assessed by 17-item Hamilton Depression Rating Scale and autobiographical memory test. The ReHo method was used to analyze regional synchronization of spontaneous neuronal activity. Patients with MDD, compared to healthy controls, exhibited extensive ReHo abnormalities in some brain regions, including the frontal, temporal, and occipital cortex. Moreover, ReHo value of the orbitofrontal cortex was negatively correlated with OGM scores in patients with MDD. The sample size of this study was relatively small, and the influence of physiological noise was not completely excluded. These results suggest that abnormal ReHo of spontaneous brain activity in the orbitofrontal cortex may be involved in the pathophysiology of OGM in patients with MDD. Copyright © 2016 Elsevier B.V. All rights reserved.

Abnormal brain synchrony in Down Syndrome☆

PubMed Central

Anderson, Jeffrey S.; Nielsen, Jared A.; Ferguson, Michael A.; Burback, Melissa C.; Cox, Elizabeth T.; Dai, Li; Gerig, Guido; Edgin, Jamie O.; Korenberg, Julie R.

2013-01-01

Down Syndrome is the most common genetic cause for intellectual disability, yet the pathophysiology of cognitive impairment in Down Syndrome is unknown. We compared fMRI scans of 15 individuals with Down Syndrome to 14 typically developing control subjects while they viewed 50 min of cartoon video clips. There was widespread increased synchrony between brain regions, with only a small subset of strong, distant connections showing underconnectivity in Down Syndrome. Brain regions showing negative correlations were less anticorrelated and were among the most strongly affected connections in the brain. Increased correlation was observed between all of the distributed brain networks studied, with the strongest internetwork correlation in subjects with the lowest performance IQ. A functional parcellation of the brain showed simplified network structure in Down Syndrome organized by local connectivity. Despite increased interregional synchrony, intersubject correlation to the cartoon stimuli was lower in Down Syndrome, indicating that increased synchrony had a temporal pattern that was not in response to environmental stimuli, but idiosyncratic to each Down Syndrome subject. Short-range, increased synchrony was not observed in a comparison sample of 447 autism vs. 517 control subjects from the Autism Brain Imaging Exchange (ABIDE) collection of resting state fMRI data, and increased internetwork synchrony was only observed between the default mode and attentional networks in autism. These findings suggest immature development of connectivity in Down Syndrome with impaired ability to integrate information from distant brain regions into coherent distributed networks. PMID:24179822

Brain single photon emission computed tomography in neonates

DOE Office of Scientific and Technical Information (OSTI.GOV)

Denays, R.; Van Pachterbeke, T.; Tondeur, M.

1989-08-01

This study was designed to rate the clinical value of ({sup 123}I)iodoamphetamine (IMP) or ({sup 99m}Tc) hexamethyl propylene amine oxyme (HM-PAO) brain single photon emission computed tomography (SPECT) in neonates, especially in those likely to develop cerebral palsy. The results showed that SPECT abnormalities were congruent in most cases with structural lesions demonstrated by ultrasonography. However, mild bilateral ventricular dilatation and bilateral subependymal porencephalic cysts diagnosed by ultrasound were not associated with an abnormal SPECT finding. In contrast, some cortical periventricular and sylvian lesions and all the parasagittal lesions well visualized in SPECT studies were not diagnosed by ultrasound scans.more » In neonates with subependymal and/or intraventricular hemorrhage the existence of a parenchymal abnormality was only diagnosed by SPECT. These results indicate that ({sup 123}I)IMP or ({sup 99m}Tc)HM-PAO brain SPECT shows a potential clinical value as the neurodevelopmental outcome is clearly related to the site, the extent, and the number of cerebral lesions. Long-term clinical follow-up is, however, mandatory in order to define which SPECT abnormality is associated with neurologic deficit.« less

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: relationships to resting-state functional connectivity

PubMed Central

Moeller, Scott J.; London, Edythe D.; Northoff, Georg

2015-01-01

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. PMID:26657968

Disrupted Structural Brain Network in AD and aMCI: A Finding of Long Fiber Degeneration.

PubMed

Fang, Rong; Yan, Xiao-Xiao; Wu, Zhi-Yuan; Sun, Yu; Yin, Qi-Hua; Wang, Ying; Tang, Hui-Dong; Sun, Jun-Feng; Miao, Fei; Chen, Sheng-Di

2015-01-01

Although recent evidence has emerged that Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) patients show both regional brain abnormalities and topological degeneration in brain networks, our understanding of the effects of white matter fiber aberrations on brain network topology in AD and aMCI is still rudimentary. In this study, we investigated the regional volumetric aberrations and the global topological abnormalities in AD and aMCI patients. The results showed a widely distributed atrophy in both gray and white matters in the AD and aMCI groups. In particular, AD patients had weaker connectivity with long fiber length than aMCI and normal control (NC) groups, as assessed by fractional anisotropy (FA). Furthermore, the brain networks of all three groups exhibited prominent economical small-world properties. Interestingly, the topological characteristics estimated from binary brain networks showed no significant group effect, indicating a tendency of preserving an optimal topological architecture in AD and aMCI during degeneration. However, significantly longer characteristic path length was observed in the FA weighted brain networks of AD and aMCI patients, suggesting dysfunctional global integration. Moreover, the abnormality of the characteristic path length was negatively correlated with the clinical ratings of cognitive impairment. Thus, the results therefore suggested that the topological alterations in weighted brain networks of AD are induced by the loss of connectivity with long fiber lengths. Our findings provide new insights into the alterations of the brain network in AD and may indicate the predictive value of the network metrics as biomarkers of disease development.

Computer-aided diagnosis of cavernous malformations in brain MR images.

PubMed

Wang, Huiquan; Ahmed, S Nizam; Mandal, Mrinal

2018-06-01

Cavernous malformation or cavernoma is one of the most common epileptogenic lesions. It is a type of brain vessel abnormality that can cause serious symptoms such as seizures, intracerebral hemorrhage, and various neurological disorders. Manual detection of cavernomas by physicians in a large set of brain MRI slices is a time-consuming and labor-intensive task and often delays diagnosis. In this paper, we propose a computer-aided diagnosis (CAD) system for cavernomas based on T2-weighted axial plane MRI image analysis. The proposed technique first extracts the brain area based on atlas registration and active contour model, and then performs template matching to obtain candidate cavernoma regions. Texture, the histogram of oriented gradients and local binary pattern features of each candidate region are calculated, and principal component analysis is applied to reduce the feature dimensionality. Support vector machines (SVMs) are finally used to classify each region into cavernoma or non-cavernoma so that most of the false positives (obtained by template matching) are eliminated. The performance of the proposed CAD system is evaluated and experimental results show that it provides superior performance in cavernoma detection compared to existing techniques. Copyright © 2018 Elsevier Ltd. All rights reserved.

Carbon Ion Irradiated Neural Injury Induced the Peripheral Immune Effects in Vitro or in Vivo

PubMed Central

Lei, Runhong; Zhao, Tuo; Li, Qiang; Wang, Xiao; Ma, Hong; Deng, Yulin

2015-01-01

Carbon ion radiation is a promising treatment for brain cancer; however, the immune system involved long-term systemic effects evoke a concern of complementary and alternative therapies in clinical treatment. To clarify radiotherapy caused fundamental changes in peripheral immune system, examinations were performed based on established models in vitro and in vivo. We found that brain-localized carbon ion radiation of neural cells induced complex changes in the peripheral blood, thymus, and spleen at one, two, and three months after its application. Atrophy, apoptosis, and abnormal T-cell distributions were observed in rats receiving a single high dose of radiation. Radiation downregulated the expression of proteins involved in T-cell development at the transcriptional level and increased the proportion of CD3+CD4−CD8+ T-cells in the thymus and the proportion of CD3+CD4+CD8− T-cells in the spleen. These data show that brain irradiation severely affects the peripheral immune system, even at relatively long times after irradiation. In addition, they provide valuable information that will implement the design of biological-based strategies that will aid brain cancer patients suffering from the long-term side effects of radiation. PMID:26633364

Disrupted Topological Patterns of Large-Scale Network in Conduct Disorder

PubMed Central

Jiang, Yali; Liu, Weixiang; Ming, Qingsen; Gao, Yidian; Ma, Ren; Zhang, Xiaocui; Situ, Weijun; Wang, Xiang; Yao, Shuqiao; Huang, Bingsheng

2016-01-01

Regional abnormalities in brain structure and function, as well as disrupted connectivity, have been found repeatedly in adolescents with conduct disorder (CD). Yet, the large-scale brain topology associated with CD is not well characterized, and little is known about the systematic neural mechanisms of CD. We employed graphic theory to investigate systematically the structural connectivity derived from cortical thickness correlation in a group of patients with CD (N = 43) and healthy controls (HCs, N = 73). Nonparametric permutation tests were applied for between-group comparisons of graphical metrics. Compared with HCs, network measures including global/local efficiency and modularity all pointed to hypo-functioning in CD, despite of preserved small-world organization in both groups. The hubs distribution is only partially overlapped with each other. These results indicate that CD is accompanied by both impaired integration and segregation patterns of brain networks, and the distribution of highly connected neural network ‘hubs’ is also distinct between groups. Such misconfiguration extends our understanding regarding how structural neural network disruptions may underlie behavioral disturbances in adolescents with CD, and potentially, implicates an aberrant cytoarchitectonic profiles in the brain of CD patients. PMID:27841320

Venous sinus occlusive disease: MR findings

DOE Office of Scientific and Technical Information (OSTI.GOV)

Yuh, W.T.C.; Simonson, T.M.; Tali, E.T.

1994-02-01

To study MR patterns of venous sinus occlusive disease and to relate them to the underlying pathophysiology by comparing the appearance and pathophysiologic features of venous sinus occlusive disease with those of arterial ischemic disease. The clinical data and MR examinations of 26 patients with venous sinus occlusive disease were retrospectively reviewed with special attention to mass effect, hemorrhage, and T2-weighted image abnormalities as well as to abnormal parenchymal, venous, or arterial enhancement after intravenous gadopentetate dimeglumine administration. Follow-up studies when available were evaluated for atrophy, infraction, chronic mass effect, and hemorrhage. Mass effect was present in 25 of 26more » patients. Eleven of the 26 had mass effect without abnormal signal on T2-weighted images. Fifteen patients had abnormal signal on T2-weighted images, but this was much less extensive than the degree of brain swelling in all cases. No patient showed abnormal parenchymal or arterial enhancement. Abnormal venous enhancement was seen in 10 of 13 patients who had contrast-enhanced studies. Intraparenchymal hemorrhage was seen in nine patients with high signal on T2-weighted images predominantly peripheral to the hematoma in eight. Three overall MR patterns were observed in acute sinus thrombosis: (1) mass effect without associated abnormal signal on T2-weighted images, (2) mass effect with associated abnormal signal on T2-weighted images and/or ventricular dilatation that may be reversible, and (3) intraparenchymal hematoma with surrounding edema. MR findings of venus sinus occlusive disease are different from those of arterial ischemia and may reflect different underlying pathophysiology. In venous sinus occlusive disease, the breakdown of the blood-brain barrier (vasogenic edema and abnormal parenchymal enhancement) does not always occur, and brain swelling can persist up to 2 years with or without abnormal signal on T2-weighted images. 34 refs., 5 figs.« less

Anatomic brain disease in hemodialysis patients: a cross-sectional study

USDA-ARS?s Scientific Manuscript database

Although dialysis patients are at high risk of stroke and have a high burden of cognitive impairment, there are few reports of anatomic brain findings in the hemodialysis population. Using magnetic resonance imaging of the brain, we compared the prevalence of brain abnormalities in hemodialysis pati...

Immunohistochemical localization of beta-amyloid precursor protein sequences in Alzheimer and normal brain tissue by light and electron microscopy.

PubMed

McGeer, P L; Akiyama, H; Kawamata, T; Yamada, T; Walker, D G; Ishii, T

1992-03-01

Immunohistochemical staining with antibodies directed against four segments of the amyloid precursor protein (APP) was studied by light and electron microscopy in normal and Alzheimer (AD) brain tissue. The segments according to the Kang et al. sequence were: 18-38 (T97); 527-540 (R36); 597-620 (1-24 of beta-amyloid protein [BAP], R17); and 681-695 (R37) (Kang et al. [1987]: Nature 325:733-736). The antibodies recognized full length APP in Western blots of extracts of APP transfected cells. They stained cytoplasmic granules in some pyramidal neurons in normal appearing tissue from control and AD cases. In AD affected tissue, the antibodies to amino terminal sections of APP stained tangled neurons and neuropil threads, and intensely stained dystrophic neurites in senile plaques. By electron microscopy, this staining was localized to abnormal filaments. The antibody to the carboxy terminal segment failed to stain neurofibrillary tangles or neuropil threads; it did stain some neurites with globular swellings. It also stained globular and elongated deposits in senile plaque areas. The antibody against the BAP intensely stained extracellular material in senile plaques and diffuse deposits. By electron microscopy, the antibodies all stained intramicroglial deposits. Some of the extracellular and intracellular BAP-positive deposits were fibrillary. Communication between intramicroglial and extracellular fibrils was detected in plaque areas. These data suggest the following sequence of events. APP is normally concentrated in intraneuronal granules. In AD, it accumulates in damaged neuronal fibers. The amino terminal portion binds to abnormal neurofilaments. Major fragments of APP are phagocytosed and processed by microglia with the BAP portion being preserved. The preserved BAP is then extruded and accumulates in extracellular tissue.

Amplitude of low frequency fluctuation abnormalities in adolescents with online gaming addiction.

PubMed

Yuan, Kai; Jin, Chenwang; Cheng, Ping; Yang, Xuejuan; Dong, Tao; Bi, Yanzhi; Xing, Lihong; von Deneen, Karen M; Yu, Dahua; Liu, Junyu; Liang, Jun; Cheng, Tingting; Qin, Wei; Tian, Jie

2013-01-01

The majority of previous neuroimaging studies have demonstrated both structural and task-related functional abnormalities in adolescents with online gaming addiction (OGA). However, few functional magnetic resonance imaging (fMRI) studies focused on the regional intensity of spontaneous fluctuations in blood oxygen level-dependent (BOLD) during the resting state and fewer studies investigated the relationship between the abnormal resting-state properties and the impaired cognitive control ability. In the present study, we employed the amplitude of low frequency fluctuation (ALFF) method to explore the local features of spontaneous brain activity in adolescents with OGA and healthy controls during resting-state. Eighteen adolescents with OGA and 18 age-, education- and gender-matched healthy volunteers participated in this study. Compared with healthy controls, adolescents with OGA showed a significant increase in ALFF values in the left medial orbitofrontal cortex (OFC), the left precuneus, the left supplementary motor area (SMA), the right parahippocampal gyrus (PHG) and the bilateral middle cingulate cortex (MCC). The abnormalities of these regions were also detected in previous addiction studies. More importantly, we found that ALFF values of the left medial OFC and left precuneus were positively correlated with the duration of OGA in adolescents with OGA. The ALFF values of the left medial OFC were also correlated with the color-word Stroop test performance. Our results suggested that the abnormal spontaneous neuronal activity of these regions may be implicated in the underlying pathophysiology of OGA.

Protecting against vascular disease in brain

PubMed Central

2011-01-01

Endothelial cells exert an enormous influence on blood vessels throughout the circulation, but their impact is particularly pronounced in the brain. New concepts have emerged recently regarding the role of this cell type and mechanisms that contribute to endothelial dysfunction and vascular disease. Activation of the renin-angiotensin system plays a prominent role in producing these abnormalities. Both oxidative stress and local inflammation are key mechanisms that underlie vascular disease of diverse etiology. Endogenous mechanisms of vascular protection are also present, including antioxidants, anti-inflammatory molecules, and peroxisome proliferator-activated receptor-γ. Despite their clear importance, studies of mechanisms that underlie cerebrovascular disease continue to lag behind studies of vascular biology in general. Identification of endogenous molecules and pathways that protect the vasculature may result in targeted approaches to prevent or slow the progression of vascular disease that causes stroke and contributes to the vascular component of dementia and Alzheimer's disease. PMID:21335467

Fetal cerebral imaging - ultrasound vs. MRI: an update.

PubMed

Blondiaux, Eléonore; Garel, Catherine

2013-11-01

The purpose of this article is to analyze the advantages and limitations of prenatal ultrasonography (US) and magnetic resonance imaging (MRI) in the evaluation of the fetal brain. These imaging modalities should not be seen as competitive but rather as complementary. There are wide variations in the world regarding screening policies, technology, skills, and legislation about termination of pregnancy, and these variations markedly impact on the way of using prenatal imaging. According to the contribution expected from each technique and to local working conditions, one should choose the most appropriate imaging modality on a case-by-case basis. The advantages and limitations of US and MRI in the setting of fetal brain imaging are displayed. Different anatomical regions (midline, ventricles, subependymal area, cerebral parenchyma, pericerebral space, posterior fossa) and pathological conditions are analyzed and illustrated in order to compare the respective contribution of each technique. An accurate prenatal diagnosis of cerebral abnormalities is of utmost importance for prenatal counseling.

Successful deep brain stimulation surgery with intraoperative magnetic resonance imaging on a difficult neuroacanthocytosis case: case report.

PubMed

Lim, Thien Thien; Fernandez, Hubert H; Cooper, Scott; Wilson, Kathryn Mary K; Machado, Andre G

2013-07-01

Chorea acanthocytosis is a progressive hereditary neurodegenerative disorder characterized by hyperkinetic movements, seizures, and acanthocytosis in the absence of any lipid abnormality. Medical treatment is typically limited and disappointing. We report on a 32-year-old patient with chorea acanthocytosis with a failed attempt at awake deep brain stimulation (DBS) surgery due to intraoperative seizures and postoperative intracranial hematoma. He then underwent a second DBS operation, but under general anesthesia and with intraoperative magnetic resonance imaging guidance. Marked improvement in his dystonia, chorea, and overall quality of life was noted 2 and 8 months postoperatively. DBS surgery of the bilateral globus pallidus pars interna may be useful in controlling the hyperkinetic movements in neuroacanthocytosis. Because of the high propensity for seizures in this disorder, DBS performed under general anesthesia, with intraoperative magnetic resonance imaging guidance, may allow successful implantation while maintaining accurate target localization.

Distortions and disconnections: disrupted brain connectivity in autism.

PubMed

Wass, Sam

2011-02-01

The past few years have seen considerable interest in findings of abnormal brain connectivity in the autism spectrum disorders (ASD). We review recent work from neuroimaging and other sources, and argue that there is considerable convergent evidence suggesting that connectivity is disrupted in ASD. We point to evidence both of local over-connectivity and of long-distance under-connectivity, and describe some non-uniformities in this picture, most notably that disruptions appear more severe in later-developing cortical regions. We conclude by discussing a number of extant questions. Firstly, we consider whether aberrant connectivity should be seen as part of the primary pathogenesis of autism, or whether disrupted connectivity in ASD emerges over time. Secondly, we consider how the patterns of disrupted connectivity found in ASD might relate to those being found in a range of other disorders. Copyright © 2010 Elsevier Inc. All rights reserved.

DYSFUNCTIONAL KYNURENINE PATHWAY METABOLISM IN THE R6/2 MOUSE MODEL OF HUNTINGTON’S DISEASE

PubMed Central

Sathyasaikumar, Korrapati V.; Stachowski, Erin K.; Amori, Laura; Guidetti, Paolo; Muchowski, Paul J.; Schwarcz, Robert

2013-01-01

Elevated concentrations of neurotoxic metabolites of the kynurenine pathway (KP) of tryptophan degradation may play a causative role in Huntington’s disease (HD). The brain levels of one of these compounds, 3-hydroxykynurenine (3-HK), are increased in both HD and several mouse models of the disease. In the present study, we examined this impairment in greater detail using the R6/2 mouse, a well-established animal model of HD. Initially, mutant and age-matched wild-type mice received an intrastriatal injection of 3H-tryptophan to assess the acute, local de novo production of kynurenine, the immediate bioprecursor of 3-HK, in vivo. No effect of genotype was observed between 4 and 12 weeks of age. In contrast, intrastriatally applied 3H-kynurenine resulted in significantly increased neosynthesis of 3H-3-HK, but not other tritiated KP metabolites, in the R6/2 striatum. Subsequent ex vivo studies in striatal, cortical and cerebellar tissue revealed substantial increases in the activity of the biosynthetic enzyme of 3-HK, kynurenine 3-monooxygenase (KMO) and significant reductions in the activity of its degradative enzyme, kynureninase, in HD mice starting at 4 weeks of age. Decreased kynureninase activity was most evident in the cortex and preceded the increase in KMO activity. The activity of other KP enzymes showed no consistent brain abnormalities in the mutant mice. These findings suggest that impairments in its immediate metabolic enzymes jointly account for the abnormally high brain levels of 3-HK in the R6/2 model of HD. PMID:20236387

Biochemical, metabolic, and behavioral characteristics of immature chronic hyperphenylalanemic rats

PubMed Central

Dienel, Gerald A.; Cruz, Nancy F.

2015-01-01

Phenylketonuria and hyperphenylalanemia are inborn errors in metabolism of phenylalanine arising from defects in steps to convert phenylalanine to tyrosine. Phe accumulation causes severe mental retardation that can be prevented by timely identification of affected individuals and their placement on a Phe-restricted diet. In spite of many studies in patients and animal models, the basis for acquisition of mental retardation during the critical period of brain development is not adequately understood. All animal models for human disease have advantages and limitations, and characteristics common to different models are most likely to correspond to the disorder. This study established similar levels of Phe exposure in developing rats between 3 and 16 days of age using three models to produce chronic hyperphenylalanemia, and identified changes in brain amino acid levels common to all models that persist for ~16h of each day. In a representative model, local rates of glucose utilization (CMRglc) were determined at 25–27 days of age, and only selective changes that appeared to depend on Phe exposure were observed. CMRglc was reduced in frontal cortex and thalamus and increased in hippocampus and globus pallidus. Behavioral testing to evaluate neuromuscular competence revealed poor performance in chronically-hyperphenylalanemic rats that persisted for at least three weeks after cessation of Phe injections and did not occur with mild or acute hyperphenylalanemia. Thus, the abnormal amino acid environment, including hyperglycinemia, in developing rat brain is associated with selective regional changes in glucose utilization and behavioral abnormalities that are not readily reversed after they are acquired. PMID:26224289

Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson’s Disease

PubMed Central

Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E.; Houle, Sylvain; Strafella, Antonio P.

2016-01-01

The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson’s disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD. PMID:27891090

Disrupted Nodal and Hub Organization Account for Brain Network Abnormalities in Parkinson's Disease.

PubMed

Koshimori, Yuko; Cho, Sang-Soo; Criaud, Marion; Christopher, Leigh; Jacobs, Mark; Ghadery, Christine; Coakeley, Sarah; Harris, Madeleine; Mizrahi, Romina; Hamani, Clement; Lang, Anthony E; Houle, Sylvain; Strafella, Antonio P

2016-01-01

The recent application of graph theory to brain networks promises to shed light on complex diseases such as Parkinson's disease (PD). This study aimed to investigate functional changes in sensorimotor and cognitive networks in Parkinsonian patients, with a focus on inter- and intra-connectivity organization in the disease-associated nodal and hub regions using the graph theoretical analyses. Resting-state functional MRI data of a total of 65 participants, including 23 healthy controls (HCs) and 42 patients, were investigated in 120 nodes for local efficiency, betweenness centrality, and degree. Hub regions were identified in the HC and patient groups. We found nodal and hub changes in patients compared with HCs, including the right pre-supplementary motor area (SMA), left anterior insula, bilateral mid-insula, bilateral dorsolateral prefrontal cortex (DLPFC), and right caudate nucleus. In general, nodal regions within the sensorimotor network (i.e., right pre-SMA and right mid-insula) displayed weakened connectivity, with the former node associated with more severe bradykinesia, and impaired integration with default mode network regions. The left mid-insula also lost its hub properties in patients. Within the executive networks, the left anterior insular cortex lost its hub properties in patients, while a new hub region was identified in the right caudate nucleus, paralleled by an increased level of inter- and intra-connectivity in the bilateral DLPFC possibly representing compensatory mechanisms. These findings highlight the diffuse changes in nodal organization and regional hub disruption accounting for the distributed abnormalities across brain networks and the clinical manifestations of PD.

Mutations in α-Tubulin Cause Abnormal Neuronal Migration in Mice and Lissencephaly in Humans

PubMed Central

Keays, David A.; Tian, Guoling; Poirier, Karine; Huang, Guo-Jen; Siebold, Christian; Cleak, James; Oliver, Peter L.; Fray, Martin; Harvey, Robert J.; Molnár, Zoltán; Piñon, Maria C.; Dear, Neil; Valdar, William; Brown, Steve D.M.; Davies, Kay E.; Rawlins, J. Nicholas P.; Cowan, Nicholas J.; Nolan, Patrick; Chelly, Jamel; Flint, Jonathan

2007-01-01

Summary The development of the mammalian brain is dependent on extensive neuronal migration. Mutations in mice and humans that affect neuronal migration result in abnormal lamination of brain structures with associated behavioral deficits. Here, we report the identification of a hyperactive N-ethyl-N-nitrosourea (ENU)-induced mouse mutant with abnormalities in the laminar architecture of the hippocampus and cortex, accompanied by impaired neuronal migration. We show that the causative mutation lies in the guanosine triphosphate (GTP) binding pocket of α-1 tubulin (Tuba1) and affects tubulin heterodimer formation. Phenotypic similarity with existing mouse models of lissencephaly led us to screen a cohort of patients with developmental brain anomalies. We identified two patients with de novo mutations in TUBA3, the human homolog of Tuba1. This study demonstrates the utility of ENU mutagenesis in the mouse as a means to discover the basis of human neurodevelopmental disorders. PMID:17218254

Beyond static measures: A review of functional magnetic resonance spectroscopy and its potential to investigate dynamic glutamatergic abnormalities in schizophrenia.

PubMed

Jelen, Luke A; King, Sinead; Mullins, Paul G; Stone, James M

2018-05-01

Abnormalities of the glutamate system are increasingly implicated in schizophrenia but their exact nature remains unknown. Proton magnetic resonance spectroscopy ( 1 H-MRS), while fundamental in revealing glutamatergic alterations in schizophrenia, has, until recently, been significantly limited and thought to only provide static measures. Functional magnetic resonance spectroscopy (fMRS), which uses sequential scans for dynamic measurement of a range of brain metabolites in activated brain areas, has lately been applied to a variety of task or stimulus conditions, producing interesting insights into neurometabolite responses to neural activation. Here, we summarise the existing 1 H-MRS studies of brain glutamate in schizophrenia. We then present a comprehensive review of research studies that have utilised fMRS, and lastly consider how fMRS methods might further the understanding of glutamatergic abnormalities in schizophrenia.

Complement inhibition by hydroxychloroquine prevents placental and fetal brain abnormalities in antiphospholipid syndrome.

PubMed

Bertolaccini, Maria Laura; Contento, Gregorio; Lennen, Ross; Sanna, Giovanni; Blower, Philip J; Ma, Michelle T; Sunassee, Kavitha; Girardi, Guillermina

2016-12-01

Placental ischemic disease and adverse pregnancy outcomes are frequently observed in patients with antiphospholipid syndrome (APS). Despite the administration of conventional antithrombotic treatment a significant number of women continue to experience adverse pregnancy outcomes, with uncertain prevention and management. Efforts to develop effective pharmacological strategies for refractory obstetric APS cases will be of significant clinical benefit for both mothers and fetuses. Although the antimalarial drug, hydroxychloroquine (HCQ) is increasingly used to treat pregnant women with APS, little is known about its efficacy and mechanism of action of HCQ. Because complement activation plays a crucial and causative role in placental ischemia and abnormal fetal brain development in APS we hypothesised that HCQ prevents these pregnancy complications through inhibition of complement activation. Using a mouse model of obstetric APS that closely resembles the clinical condition, we found that HCQ prevented fetal death and the placental metabolic changes -measured by proton magnetic resonance spectroscopy in APS-mice. Using 111 In labelled antiphospholipid antibodies (aPL) we identified the placenta and the fetal brain as the main organ targets in APS-mice. Using this same method, we found that HCQ does not inhibit aPL binding to tissues as was previously suggested from in vitro studies. While HCQ did not affect aPL binding to fetal brain it prevented fetal brain abnormal cortical development. HCQ prevented complement activation in vivo and in vitro. Complement C5a levels in serum samples from APS patients and APS-mice were lower after treatment with HCQ while the antibodies titres remained unchanged. HCQ prevented not only placental insufficiency but also abnormal fetal brain development in APS. By inhibiting complement activation, HCQ might also be an effective antithrombotic therapy. Copyright © 2016 Elsevier Ltd. All rights reserved.

Brain magnetic resonance imaging findings in Smith-Lemli-Opitz syndrome.

PubMed

Lee, Ryan W Y; Conley, Sandra K; Gropman, Andrea; Porter, Forbes D; Baker, Eva H

2013-10-01

Smith-Lemli-Opitz syndrome (SLOS) is a neurodevelopmental disorder caused by inborn errors of cholesterol metabolism resulting from mutations in 7-dehydrocholesterol reductase (DHCR7). There are only a few studies describing the brain imaging findings in SLOS. This study examines the prevalence of magnetic resonance imaging (MRI) abnormalities in the largest cohort of patients with SLOS to date. Fifty-five individuals with SLOS (27 M, 28 F) between age 0.17 years and 25.4 years (mean = 6.2, SD = 5.8) received a total of 173 brain MRI scans (mean = 3.1 per subject) on a 1.5T GE scanner between September 1998 and December 2003, or on a 3T Philips scanner between October 2010 and September 2012; all exams were performed at the Clinical Center of the National Institutes of Health. We performed a retrospective review of these imaging studies for both major and minor brain anomalies. Aberrant MRI findings were observed in 53 of 55 (96%) SLOS patients, with abnormalities of the septum pellucidum the most frequent (42/55, 76%) finding. Abnormalities of the corpus callosum were found in 38 of 55 (69%) patients. Other findings included cerebral atrophy, cerebellar atrophy, colpocephaly, white matter lesions, arachnoid cysts, Dandy-Walker variant, and type I Chiari malformation. Significant correlations were observed when comparing MRI findings with sterol levels and somatic malformations. Individuals with SLOS commonly have anomalies involving the midline and para-midline structures of the brain. Further studies are required to examine the relationship between structural brain abnormalities and neurodevelopmental disability in SLOS. © 2013 The Authors. American Journal of Medical Genetics Part A Published by U.S. Government Work.

Abnormal regional cerebral blood flow in childhood autism.

PubMed

Ohnishi, T; Matsuda, H; Hashimoto, T; Kunihiro, T; Nishikawa, M; Uema, T; Sasaki, M

2000-09-01

Neuroimaging studies of autism have shown abnormalities in the limbic system and cerebellar circuits and additional sites. These findings are not, however, specific or consistent enough to build up a coherent theory of the origin and nature of the brain abnormality in autistic patients. Twenty-three children with infantile autism and 26 non-autistic controls matched for IQ and age were examined using brain-perfusion single photon emission computed tomography with technetium-99m ethyl cysteinate dimer. In autistic subjects, we assessed the relationship between regional cerebral blood flow (rCBF) and symptom profiles. Images were anatomically normalized, and voxel-by-voxel analyses were performed. Decreases in rCBF in autistic patients compared with the control group were identified in the bilateral insula, superior temporal gyri and left prefrontal cortices. Analysis of the correlations between syndrome scores and rCBF revealed that each syndrome was associated with a specific pattern of perfusion in the limbic system and the medial prefrontal cortex. The results confirmed the associations of (i) impairments in communication and social interaction that are thought to be related to deficits in the theory of mind (ToM) with altered perfusion in the medial prefrontal cortex and anterior cingulate gyrus, and (ii) the obsessive desire for sameness with altered perfusion in the right medial temporal lobe. The perfusion abnormalities seem to be related to the cognitive dysfunction observed in autism, such as deficits in ToM, abnormal responses to sensory stimuli, and the obsessive desire for sameness. The perfusion patterns suggest possible locations of abnormalities of brain function underlying abnormal behaviour patterns in autistic individuals.

Structural and behavioral correlates of abnormal encoding of money value in the sensorimotor striatum in cocaine addiction.

PubMed

Konova, Anna B; Moeller, Scott J; Tomasi, Dardo; Parvaz, Muhammad A; Alia-Klein, Nelly; Volkow, Nora D; Goldstein, Rita Z

2012-10-01

Abnormalities in frontostriatal systems are thought to be central to the pathophysiology of addiction, and may underlie the maladaptive processing of the highly generalizable reinforcer, money. Although abnormal frontostriatal structure and function have been observed in individuals addicted to cocaine, it is less clear how individual variability in brain structure is associated with brain function to influence behavior. Our objective was to examine frontostriatal structure and neural processing of money value in chronic cocaine users and closely matched healthy controls. A reward task that manipulated different levels of money was used to isolate neural activity associated with money value. Gray matter volume measures were used to assess frontostriatal structure. Our results indicated that cocaine users had an abnormal money value signal in the sensorimotor striatum (right putamen/globus pallidus) that was negatively associated with accuracy adjustments to money and was more pronounced in individuals with more severe use. In parallel, group differences were also observed in both the function and gray matter volume of the ventromedial prefrontal cortex; in the cocaine users, the former was directly associated with response to money in the striatum. These results provide strong evidence for abnormalities in the neural mechanisms of valuation in addiction and link these functional abnormalities with deficits in brain structure. In addition, as value signals represent acquired associations, their abnormal processing in the sensorimotor striatum, a region centrally implicated in habit formation, could signal disadvantageous associative learning in cocaine addiction. © 2012 Published 2012. This article is a US Government work and is in the public domain in the USA.

Patterns of chronic venous insufficiency in the dural sinuses and extracranial draining veins and their relationship with white matter hyperintensities for patients with Parkinson's disease.

PubMed

Liu, Manju; Xu, Haibo; Wang, Yuhui; Zhong, Yi; Xia, Shuang; Utriainen, David; Wang, Tao; Haacke, E Mark

2015-06-01

Idiopathic Parkinson's disease (IPD) remains one of those neurodegenerative diseases for which the cause remains unknown. Many clinically diagnosed cases of IPD are associated with cerebrovascular disease and white matter hyperintensities (WMHs). The purpose of this study was to investigate the presence of transverse sinus and extracranial venous abnormalities in IPD patients and their relationship with brain WMHs. Twenty-three IPD patients and 23 age-matched normal controls were recruited in this study. They had conventional neurologic magnetic resonance structural and angiographic scans and, for blood flow, quantification of the extracranial vessels. Venous structures were evaluated with two-dimensional time of flight; flow was evaluated with two-dimensional phase contrast; and WMH volume was quantified with T2-weighted fluid-attenuated inversion recovery. The IPD and normal subjects were classified by both the magnetic resonance time-of-flight and phase contrast images into four categories: (1) complete or local missing transverse sinus and internal jugular veins on the time-of-flight images; (2) low flow in the transverse sinus and stenotic internal jugular veins; (3) reduced flow in the internal jugular veins; and (4) normal flow and no stenosis. Broken into the four categories with categories 1 to 3 combined, a significant difference in the distribution of the IPD patients and normal controls (χ(2) = 7.7; P < .01) was observed. Venous abnormalities (categories 1, 2, and 3) were seen in 57% of IPD subjects and in only 30% of controls. In IPD subjects, category type correlated with both flow abnormalities and WMHs. From this preliminary study, we conclude that a major fraction of IPD patients appear to have abnormal venous anatomy and flow on the left side of the brain and neck and that the flow abnormalities appear to correlate with WMH volume. Studies with a larger sample size are still needed to confirm these findings. Copyright © 2015 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.

Genetic control of postnatal human brain growth

PubMed Central

van Dyck, Laura I.; Morrow, Eric M.

2017-01-01

Purpose of review Studies investigating postnatal brain growth disorders inform the biology underlying the development of human brain circuitry. This research is becoming increasingly important for the diagnosis and treatment of childhood neurodevelopmental disorders, including autism and related disorders. Here we review recent research on typical and abnormal postnatal brain growth and examine potential biological mechanisms. Recent findings Clinically, brain growth disorders are heralded by diverging head size for a given age and sex, but are more precisely characterized by brain imaging, postmortem analysis, and animal model studies. Recent neuroimaging and molecular biological studies on postnatal brain growth disorders have broadened our view of both typical and pathological postnatal neurodevelopment. Correlating gene and protein function with brain growth trajectories uncovers postnatal biological mechanisms, including neuronal arborization, synaptogenesis and pruning, and gliogenesis and myelination. Recent investigations of childhood neurodevelopmental and neurodegenerative disorders highlight the underlying genetic programming and experience-dependent remodeling of neural circuitry. Summary In order to understand typical and abnormal postnatal brain development, clinicians and researchers should characterize brain growth trajectories in the context of neurogenetic syndromes. Understanding mechanisms and trajectories of postnatal brain growth will aid in differentiating, diagnosing, and potentially treating neurodevelopmental disorders. PMID:27898583

Pharmacological imaging as a tool to visualise dopaminergic neurotoxicity.

PubMed

Schrantee, A; Reneman, L

2014-09-01

Dopamine abnormalities underlie a wide variety of psychopathologies, including ADHD and schizophrenia. A new imaging technique, pharmacological magnetic resonance imaging (phMRI), is a promising non-invasive technique to visualize the dopaminergic system in the brain. In this review we explore the clinical potential of phMRI in detecting dopamine dysfunction or neurotoxicity, assess its strengths and weaknesses and identify directions for future research. Preclinically, phMRI is able to detect severe dopaminergic abnormalities quite similar to conventional techniques such as PET and SPECT. phMRI benefits from its high spatial resolution and the possibility to visualize both local and downstream effects of dopaminergic neurotransmission. In addition, it allows for repeated measurements and assessments in vulnerable populations. The major challenge is the complex interpretation of phMRI results. Future studies in patients with dopaminergic abnormalities need to confirm the currently reviewed preclinical findings to validate the technique in a clinical setting. Eventually, based on the current review we expect that phMRI can be of use in a clinical setting involving vulnerable populations (such as children and adolescents) for diagnosis and monitoring treatment efficacy. This article is part of the Special Issue Section entitled 'Neuroimaging in Neuropharmacology'. Copyright © 2013 Elsevier Ltd. All rights reserved.

New animal models to study the role of tyrosinase in normal retinal development.

PubMed

Lavado, Alfonso; Montoliu, Lluis

2006-01-01

Albino animals display a hypopigmented phenotype associated with several visual abnormalities, including rod photoreceptor cell deficits, abnormal patterns of connections between the eye and the brain and a general underdevelopment of central retina. Oculocutaneous albinism type I, a common form of albinism, is caused by mutations in the tyrosinase gene. In mice, the albino phenotype can be corrected by functional tyrosinase transgenes. Tyrosinase transgenic animals not only show normal pigmentation but the correction of all visual abnormalities associated with albinism, confirming a role of tyrosinase, a key enzyme in melanin biosynthesis, in normal retinal development. Here, we will discuss recent work carried out with new tyrosinase transgenic mouse models, to further analyse the role of tyrosinase in retinal development. We will first report a transgenic model with inducible tyrosinase expression that has been used to address the regulated activation of this gene and its associated effects on the development of the visual system. Second, we will comment on an interesting yeast artificial chromosome (YAC)-tyrosinase transgene, lacking important regulatory elements, that has highlighted the significance of local interactions between the retinal pigment epithelium (RPE) and developing neural retina.

Cranial mononeuropathy III

MedlinePlus

... is one of the cranial nerves that control eye movement. Causes may include: Brain aneurysm Infections Abnormal blood ... show: Enlarged (dilated) pupil of the affected eye Eye movement abnormalities Eyes that are not aligned Your health ...

Addiction Related Alteration in Resting-state Brain Connectivity

PubMed Central

Ma, Ning; Liu, Ying; Li, Nan; Wang, Chang-Xin; Zhang, Hao; Jiang, Xiao-Feng; Xu, Hu-Sheng; Fu, Xian-Ming; Hu, Xiaoping; Zhang, Da-Ren

2009-01-01

It is widely accepted that addictive drug use is related to abnormal functional organization in the user’s brain. The present study aimed to identify this type of abnormality within the brain networks implicated in addiction by resting-state functional connectivity measured with functional magnetic resonance imaging (fMRI). With fMRI data acquired during resting state from 14 chronic heroin users (12 of whom were being treated with methadone) and 13 non-addicted controls, we investigated the addiction related alteration in functional connectivity between the regions in the circuits implicated in addiction with seed-based correlation analysis. Compared with controls, chronic heroin users showed increased functional connectivity between nucleus accumbens and ventral/rostral anterior cingulate cortex (ACC), and orbital frontal cortex (OFC), between amygdala and OFC; and reduced functional connectivity between prefrontal cortex and OFC, and ACC. These observations of altered resting-state functional connectivity suggested abnormal functional organization in the addicted brain and may provide additional evidence supporting the theory of addiction that emphasizes enhanced salience value of a drug and its related cues but weakened cognitive control in the addictive state. PMID:19703568

Fluorescent nanodiamond tracking reveals intraneuronal transport abnormalities induced by brain-disease-related genetic risk factors

NASA Astrophysics Data System (ADS)

Haziza, Simon; Mohan, Nitin; Loe-Mie, Yann; Lepagnol-Bestel, Aude-Marie; Massou, Sophie; Adam, Marie-Pierre; Le, Xuan Loc; Viard, Julia; Plancon, Christine; Daudin, Rachel; Koebel, Pascale; Dorard, Emilie; Rose, Christiane; Hsieh, Feng-Jen; Wu, Chih-Che; Potier, Brigitte; Herault, Yann; Sala, Carlo; Corvin, Aiden; Allinquant, Bernadette; Chang, Huan-Cheng; Treussart, François; Simonneau, Michel

2017-05-01

Brain diseases such as autism and Alzheimer's disease (each inflicting >1% of the world population) involve a large network of genes displaying subtle changes in their expression. Abnormalities in intraneuronal transport have been linked to genetic risk factors found in patients, suggesting the relevance of measuring this key biological process. However, current techniques are not sensitive enough to detect minor abnormalities. Here we report a sensitive method to measure the changes in intraneuronal transport induced by brain-disease-related genetic risk factors using fluorescent nanodiamonds (FNDs). We show that the high brightness, photostability and absence of cytotoxicity allow FNDs to be tracked inside the branches of dissociated neurons with a spatial resolution of 12 nm and a temporal resolution of 50 ms. As proof of principle, we applied the FND tracking assay on two transgenic mouse lines that mimic the slight changes in protein concentration (∼30%) found in the brains of patients. In both cases, we show that the FND assay is sufficiently sensitive to detect these changes.

Significance of abnormalities in developmental trajectory and asymmetry of cortical serotonin synthesis in autism.

PubMed

Chandana, Sreenivasa R; Behen, Michael E; Juhász, Csaba; Muzik, Otto; Rothermel, Robert D; Mangner, Thomas J; Chakraborty, Pulak K; Chugani, Harry T; Chugani, Diane C

2005-01-01

The role of serotonin in prenatal and postnatal brain development is well documented in the animal literature. In earlier studies using positron emission tomography (PET) with the tracer alpha[(11)C]methyl-l-tryptophan (AMT), we reported global and focal abnormalities of serotonin synthesis in children with autism. In the present study, we measured brain serotonin synthesis in a large group of autistic children (n = 117) with AMT PET and related these neuroimaging data to handedness and language function. Cortical AMT uptake abnormalities were objectively derived from small homotopic cortical regions using a predefined cutoff asymmetry threshold (>2 S.D. of normal asymmetry). Autistic children demonstrated several patterns of abnormal cortical involvement, including right cortical, left cortical, and absence of abnormal asymmetry. Global brain values for serotonin synthesis capacity (unidirectional uptake rate constant, K-complex) values were plotted as a function of age. K-complex values of autistic children with asymmetry or no asymmetry in cortical AMT uptake followed different developmental patterns, compared to that of a control group of non-autistic children. The autism groups, defined by presence or absence and side of cortical asymmetry, differed on a measure of language as well as handedness. Autistic children with left cortical AMT decreases showed a higher prevalence of severe language impairment, whereas those with right cortical decreases showed a higher prevalence of left and mixed handedness. Global as well as focal abnormally asymmetric development in the serotonergic system could lead to miswiring of the neural circuits specifying hemispheric specialization.

Postmortem brain abnormalities of the glutamate neurotransmitter system in autism.

PubMed

Purcell, A E; Jeon, O H; Zimmerman, A W; Blue, M E; Pevsner, J

2001-11-13

Studies examining the brains of individuals with autism have identified anatomic and pathologic changes in regions such as the cerebellum and hippocampus. Little, if anything, is known, however, about the molecules that are involved in the pathogenesis of this disorder. To identify genes with abnormal expression levels in the cerebella of subjects with autism. Brain samples from a total of 10 individuals with autism and 23 matched controls were collected, mainly from the cerebellum. Two cDNA microarray technologies were used to identify genes that were significantly up- or downregulated in autism. The abnormal mRNA or protein levels of several genes identified by microarray analysis were investigated using PCR with reverse transcription and Western blotting. alpha-Amino-3-hydroxy-5-methyl-4-isoxazoleproprionic acid (AMPA)- and NMDA-type glutamate receptor densities were examined with receptor autoradiography in the cerebellum, caudate-putamen, and prefrontal cortex. The mRNA levels of several genes were significantly increased in autism, including excitatory amino acid transporter 1 and glutamate receptor AMPA 1, two members of the glutamate system. Abnormalities in the protein or mRNA levels of several additional molecules in the glutamate system were identified on further analysis, including glutamate receptor binding proteins. AMPA-type glutamate receptor density was decreased in the cerebellum of individuals with autism (p < 0.05). Subjects with autism may have specific abnormalities in the AMPA-type glutamate receptors and glutamate transporters in the cerebellum. These abnormalities may be directly involved in the pathogenesis of the disorder.

Pharmacotherapeutics directed at deficiencies associated with cocaine dependence: Focus on dopamine, norepinephrine and glutamate

PubMed Central

Haile, Colin N.; Mahoney, James J.; Newton, Thomas F.; De La Garza, Richard

2012-01-01

Much effort has been devoted to research focused on pharmacotherapies for cocaine dependence yet there are no FDA-approved medications for this brain disease. Preclinical models have been essential to defining the central and peripheral effects produced by cocaine. Recent evidence suggests that cocaine exerts its reinforcing effects by acting on multiple neurotransmitter systems within mesocorticolimibic circuitry. Imaging studies in cocaine-dependent individuals have identified deficiencies in dopaminergic signaling primarily localized to corticolimbic areas. In addition to dysregulated striatal dopamine, norepinephrine and glutamate are also altered in cocaine dependence. In this review, we present these brain abnormalities as therapeutic targets for the treatment of cocaine dependence. We then survey promising medications that exert their therapeutic effects by presumably ameliorating these brain deficiencies. Correcting neurochemical deficits in cocaine-dependent individuals improves memory and impulse control, and reduces drug craving that may decrease cocaine use. We hypothesize that using medications aimed at reversing known neurochemical imbalances is likely to be more productive than current approaches. This view is also consistent with treatment paradigms used in neuropsychiatry and general medicine. PMID:22327234

Biomarkers and Stimulation Algorithms for Adaptive Brain Stimulation

PubMed Central

Hoang, Kimberly B.; Cassar, Isaac R.; Grill, Warren M.; Turner, Dennis A.

2017-01-01

The goal of this review is to describe in what ways feedback or adaptive stimulation may be delivered and adjusted based on relevant biomarkers. Specific treatment mechanisms underlying therapeutic brain stimulation remain unclear, in spite of the demonstrated efficacy in a number of nervous system diseases. Brain stimulation appears to exert widespread influence over specific neural networks that are relevant to specific disease entities. In awake patients, activation or suppression of these neural networks can be assessed by either symptom alleviation (i.e., tremor, rigidity, seizures) or physiological criteria, which may be predictive of expected symptomatic treatment. Secondary verification of network activation through specific biomarkers that are linked to symptomatic disease improvement may be useful for several reasons. For example, these biomarkers could aid optimal intraoperative localization, possibly improve efficacy or efficiency (i.e., reduced power needs), and provide long-term adaptive automatic adjustment of stimulation parameters. Possible biomarkers for use in portable or implanted devices span from ongoing physiological brain activity, evoked local field potentials (LFPs), and intermittent pathological activity, to wearable devices, biochemical, blood flow, optical, or magnetic resonance imaging (MRI) changes, temperature changes, or optogenetic signals. First, however, potential biomarkers must be correlated directly with symptom or disease treatment and network activation. Although numerous biomarkers are under consideration for a variety of stimulation indications the feasibility of these approaches has yet to be fully determined. Particularly, there are critical questions whether the use of adaptive systems can improve efficacy over continuous stimulation, facilitate adjustment of stimulation interventions and improve our understanding of the role of abnormal network function in disease mechanisms. PMID:29066947

Functional Brain Imaging

PubMed Central

2006-01-01

Executive Summary Objective The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer’s disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson’s disease (PD). Clinical Need: Target Population and Condition Alzheimer’s disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson’s disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. The Technology Being Reviewed Functional Brain Imaging Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. Review Strategy The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS’), and retrospective studies. Sample sizes of at least 20 patients (≥ 10 with condition being reviewed). English-language studies. Human studies. Any age. Studying at least one of the following: fMRI, PET, MRS, or MEG. Functional brain imaging modality must be compared with a clearly defined reference standard. Must report at least one of the following outcomes: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. Summary of Findings There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-18F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS. PMID:23074493

Functional brain imaging: an evidence-based analysis.

PubMed

2006-01-01

The objective of this analysis is to review a spectrum of functional brain imaging technologies to identify whether there are any imaging modalities that are more effective than others for various brain pathology conditions. This evidence-based analysis reviews magnetoencephalography (MEG), magnetic resonance spectroscopy (MRS), positron emission tomography (PET), and functional magnetic resonance imaging (fMRI) for the diagnosis or surgical management of the following conditions: Alzheimer's disease (AD), brain tumours, epilepsy, multiple sclerosis (MS), and Parkinson's disease (PD). TARGET POPULATION AND CONDITION Alzheimer's disease is a progressive, degenerative, neurologic condition characterized by cognitive impairment and memory loss. The Canadian Study on Health and Aging estimated that there will be 97,000 incident cases (about 60,000 women) of dementia (including AD) in Canada in 2006. In Ontario, there will be an estimated 950 new cases and 580 deaths due to brain cancer in 2006. Treatments for brain tumours include surgery and radiation therapy. However, one of the limitations of radiation therapy is that it damages tissue though necrosis and scarring. Computed tomography (CT) and magnetic resonance imaging (MRI) may not distinguish between radiation effects and resistant tissue, creating a potential role for functional brain imaging. Epilepsy is a chronic disorder that provokes repetitive seizures. In Ontario, the rate of epilepsy is estimated to be 5 cases per 1,000 people. Most people with epilepsy are effectively managed with drug therapy; but about 50% do not respond to drug therapy. Surgical resection of the seizure foci may be considered in these patients, and functional brain imaging may play a role in localizing the seizure foci. Multiple sclerosis is a progressive, inflammatory, demyelinating disease of the central nervous system (CNS). The cause of MS is unknown; however, it is thought to be due to a combination of etiologies, including genetic and environmental components. The prevalence of MS in Canada is 240 cases per 100,000 people. Parkinson's disease is the most prevalent movement disorder; it affects an estimated 100,000 Canadians. Currently, the standard for measuring disease progression is through the use of scales, which are subjective measures of disease progression. Functional brain imaging may provide an objective measure of disease progression, differentiation between parkinsonian syndromes, and response to therapy. FUNCTIONAL BRAIN IMAGING: Functional brain imaging technologies measure blood flow and metabolism. The results of these tests are often used in conjunction with structural imaging (e.g., MRI or CT). Positron emission tomography and MRS identify abnormalities in brain tissues. The former measures abnormalities through uptake of radiotracers in the brain, while the latter measures chemical shifts in metabolite ratios to identify abnormalities. The potential role of functional MRI (fMRI) is to identify the areas of the brain responsible for language, sensory and motor function (sensorimotor cortex), rather than identifying abnormalities in tissues. Magnetoencephalography measures magnetic fields of the electric currents in the brain, identifying aberrant activity. Magnetoencephalography may have the potential to localize seizure foci and to identify the sensorimotor cortex, visual cortex and auditory cortex. In terms of regulatory status, MEG and PET are licensed by Health Canada. Both MRS and fMRI use a MRI platform; thus, they do not have a separate licence from Health Canada. The radiotracers used in PET scanning are not licensed by Health Canada for general use but can be used through a Clinical Trials Application. The literature published up to September 2006 was searched in the following databases: MEDLINE, MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Cochrane Database of Systematic Reviews, CENTRAL, and International Network of Agencies for Health Technology Assessment (INAHTA). The database search was supplemented with a search of relevant Web sites and a review of the bibliographies of selected papers. General inclusion criteria were applied to all conditions. Those criteria included the following: Full reports of systematic reviews, randomized controlled trials (RCTs), cohort-control studies, prospective cohort studies (PCS'), and retrospective studies.Sample sizes of at least 20 patients (≥ 10 with condition being reviewed).English-language studies.Human studies.Any age.STUDYING AT LEAST ONE OF THE FOLLOWING: fMRI, PET, MRS, or MEG.Functional brain imaging modality must be compared with a clearly defined reference standard.MUST REPORT AT LEAST ONE OF THE FOLLOWING OUTCOMES: sensitivity, specificity, accuracy, positive predictive value (PPV), receiver operating characteristic curve, outcome measuring impact on diagnostic testing, treatment, patient health, or cost. There is evidence to indicate that PET can accurately diagnose AD; however, at this time, there is no evidence to suggest that a diagnosis of AD with PET alters the clinical outcomes of patients. The addition of MRS or O-(2-(18)F-Fluoroethyl)-L-Tyrosine (FET)-PET to gadolinium (Gd)-enhanced MRI for distinguishing malignant from benign tumours during primary diagnosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients to distinguish malignant from benign tumours is unclear, because patients with a suspected brain tumour will likely undergo a biopsy despite additional imaging results. The addition of MRS, FET-PET, or MRI T2 to Gd-enhanced MRI for the differentiation of recurrence from radiation necrosis may provide a higher specificity than Gd-enhanced MRI alone. The clinical utility of additional imaging in patients with a suspected recurrence is in the monitoring of patients. Based on the evidence available, it is unclear if one of the imaging modalities (MRS, FET-PET, or MRI T2) offers significantly improved specificity over another. There may be a role for fMRI in the identification of surgical candidates for tumour resection; however, this requires further research. Based on the studies available, it is unclear if MEG has similar accuracy in localizing seizure foci to intracranial electroencephalogram (ICEEG). More high-quality research is needed to establish whether there is a difference in accuracy between MEG and ICEEG. The results of the studies comparing PET to noninvasive electroencephalogram (EEG) did not demonstrate that PET was more accurate at localizing seizure foci; however, there may be some specific conditions, such as tuberous sclerosis, where PET may be more accurate than noninvasive EEG. There may be some clinical utility for MEG or fMRI in presurgical functional mapping; however, this needs further investigation involving comparisons with other modalities. The clinical utility of MRS has yet to be established for patients with epilepsy. Positron emission tomography has high sensitivity and specificity in the diagnosis of PD and the differential diagnosis of parkinsonian syndromes; however, it is unclear at this time if the addition of PET in the diagnosis of these conditions contributes to the treatment and clinical outcomes of patients. There is limited clinical utility of functional brain imaging in the management of patients with MS at this time. Diagnosis of MS is established through clinical history, evoked potentials, and MRI. Magnetic resonance imaging can identify the multifocal white lesions and other structural characteristics of MS.

Abnormal electroretinogram associated with developmental brain anomalies.

PubMed Central

Cibis, G W; Fitzgerald, K M

1995-01-01

PURPOSE: We have encountered abnormal ERGs associated with optic nerve hypoplasia, macular, optic nerve and chorioretinal colobomata and developmental brain anomalies. Brain anomalies include cortical dysgenesis, lissencephaly, porencephaly, cerebellar and corpus callosum hypoplasia. We describe six exemplar cases. METHODS: Scotopic and photopic ERGs adherent to international standards were performed as well as photopic ERGs to long-duration stimuli. CT or MRI studies were also done. The ERGs were compared to age-matched normal control subjects. RESULTS: ERG changes include reduced amplitude b-waves to blue and red stimuli under scotopic testing conditions. Implicit times were often delayed. The photopic responses also showed reduced amplitude a- and b-waves with implicit time delays. The long-duration photopic ERG done in one case shows attenuation of both ON- and OFF-responses. CONCLUSIONS: Common underlying developmental genetic or environmental unifying casualties are speculated to be at fault in causing these cases of associated retinal and brain abnormalities. No single etiology is expected. Multiple potential causes acting early in embryogenesis effecting neuronal induction, migration and differentiation are theorized. These occur at a time when brain and retinal cells are sufficiently undifferentiated to be similarly effected. We call these cases examples of Brain Retina Neuroembryodysgenesis (BRNED). Homeobox and PAX genes with global neuronal developmental influences are gene candidates to unify the observed disruption of brain and retinal cell development. The ERG can provide a valuable clinical addition in understanding and ultimately classifying these disorders. Images FIGURE 1 FIGURE 4 FIGURE 5 FIGURE 6 FIGURE 7 FIGURE 8 PMID:8719676

Connectivity and functional profiling of abnormal brain structures in pedophilia

PubMed Central

Poeppl, Timm B.; Eickhoff, Simon B.; Fox, Peter T.; Laird, Angela R.; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-01-01

Despite its 0.5–1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multi-modal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. PMID:25733379

Connectivity and functional profiling of abnormal brain structures in pedophilia.

PubMed

Poeppl, Timm B; Eickhoff, Simon B; Fox, Peter T; Laird, Angela R; Rupprecht, Rainer; Langguth, Berthold; Bzdok, Danilo

2015-06-01

Despite its 0.5-1% lifetime prevalence in men and its general societal relevance, neuroimaging investigations in pedophilia are scarce. Preliminary findings indicate abnormal brain structure and function. However, no study has yet linked structural alterations in pedophiles to both connectional and functional properties of the aberrant hotspots. The relationship between morphological alterations and brain function in pedophilia as well as their contribution to its psychopathology thus remain unclear. First, we assessed bimodal connectivity of structurally altered candidate regions using meta-analytic connectivity modeling (MACM) and resting-state correlations employing openly accessible data. We compared the ensuing connectivity maps to the activation likelihood estimation (ALE) maps of a recent quantitative meta-analysis of brain activity during processing of sexual stimuli. Second, we functionally characterized the structurally altered regions employing meta-data of a large-scale neuroimaging database. Candidate regions were functionally connected to key areas for processing of sexual stimuli. Moreover, we found that the functional role of structurally altered brain regions in pedophilia relates to nonsexual emotional as well as neurocognitive and executive functions, previously reported to be impaired in pedophiles. Our results suggest that structural brain alterations affect neural networks for sexual processing by way of disrupted functional connectivity, which may entail abnormal sexual arousal patterns. The findings moreover indicate that structural alterations account for common affective and neurocognitive impairments in pedophilia. The present multimodal integration of brain structure and function analyses links sexual and nonsexual psychopathology in pedophilia. © 2015 Wiley Periodicals, Inc.

[Eating disorders].

PubMed

Miyake, Yoshie; Okamoto, Yuri; Jinnin, Ran; Shishida, Kazuhiro; Okamoto, Yasumasa

2015-02-01

Eating disorders are characterized by aberrant patterns of eating behavior, including such symptoms as extreme restriction of food intake or binge eating, and severe disturbances in the perception of body shape and weight, as well as a drive for thinness and obsessive fears of becoming fat. Eating disorder is an important cause for physical and psychosocial morbidity in young women. Patients with eating disorders have a deficit in the cognitive process and functional abnormalities in the brain system. Recently, brain-imaging techniques have been used to identify specific brain areas that function abnormally in patients with eating disorders. We have discussed the clinical and cognitive aspects of eating disorders and summarized neuroimaging studies of eating disorders.

Neuroimaging of Narcolepsy and Kleine-Levin Syndrome.

PubMed

Hong, Seung Bong

2017-09-01

Narcolepsy is a chronic neurologic disorder with the abnormal regulation of the sleep-wake cycle, resulting in excessive daytime sleepiness, disturbed nocturnal sleep, and manifestations related to rapid eye movement sleep, such as cataplexy, sleep paralysis, and hypnagogic hallucination. Over the past decade, numerous neuroimaging studies have been performed to characterize the pathophysiology and various clinical features of narcolepsy. This article reviews structural and functional brain imaging findings in narcolepsy and Kleine-Levin syndrome. Based on the current state of research, brain imaging is a useful tool to investigate and understand the neuroanatomic correlates and brain abnormalities of narcolepsy and other hypersomnia. Copyright © 2017 Elsevier Inc. All rights reserved.

Cobalt-55 positron emission tomography in traumatic brain injury: a pilot study.

PubMed Central

Jansen, H M; van der Naalt, J; van Zomeren, A H; Paans, A M; Veenma-van der Duin, L; Hew, J M; Pruim, J; Minderhoud, J M; Korf, J

1996-01-01

Traumatic brain injury is usually assessed with the Glasgow coma scale (GCS), CT, or MRI. After such injury, the injured brain tissue is characterised by calcium mediated neuronal damage and inflammation. Positron emission tomography with the isotope cobalt-55 (Co-PET) as a calcium tracer enables imaging of affected tissue in traumatic brain injury. The aim was to determine whether additional information can be gained by Co-PET in the diagnosis of moderate traumatic brain injury and to assess any prognostic value of Co-PET. Five patients with recent moderately severe traumatic brain injury were studied. CT was performed on the day of admission, EEG within one week, and MRI and Co-PET within four weeks of injury. Clinical assessment included neurological examination, GCS, neuropsychological testing, and Glasgow outcome scale (GOS) after one year. Co-PET showed focal uptake that extended beyond the morphological abnormalities shown by MRI and CT, in brain regions that were actually diagnosed with EEG. Thus Co-PET is potentially useful for diagnostic localisation of both structural and functional abnormalities in moderate traumatic brain injury. Images PMID:8708661

Application of an enhanced fuzzy algorithm for MR brain tumor image segmentation

NASA Astrophysics Data System (ADS)

Hemanth, D. Jude; Vijila, C. Kezi Selva; Anitha, J.

2010-02-01

Image segmentation is one of the significant digital image processing techniques commonly used in the medical field. One of the specific applications is tumor detection in abnormal Magnetic Resonance (MR) brain images. Fuzzy approaches are widely preferred for tumor segmentation which generally yields superior results in terms of accuracy. But most of the fuzzy algorithms suffer from the drawback of slow convergence rate which makes the system practically non-feasible. In this work, the application of modified Fuzzy C-means (FCM) algorithm to tackle the convergence problem is explored in the context of brain image segmentation. This modified FCM algorithm employs the concept of quantization to improve the convergence rate besides yielding excellent segmentation efficiency. This algorithm is experimented on real time abnormal MR brain images collected from the radiologists. A comprehensive feature vector is extracted from these images and used for the segmentation technique. An extensive feature selection process is performed which reduces the convergence time period and improve the segmentation efficiency. After segmentation, the tumor portion is extracted from the segmented image. Comparative analysis in terms of segmentation efficiency and convergence rate is performed between the conventional FCM and the modified FCM. Experimental results show superior results for the modified FCM algorithm in terms of the performance measures. Thus, this work highlights the application of the modified algorithm for brain tumor detection in abnormal MR brain images.

Multimodality Instrument for Tissue Characterization

NASA Technical Reports Server (NTRS)

Mah, Robert W. (Inventor); Andrews, Russell J. (Inventor)

2000-01-01

A system with multimodality instrument for tissue identification includes a computer-controlled motor driven heuristic probe with a multisensory tip is discussed. For neurosurgical applications, the instrument is mounted on a stereotactic frame for the probe to penetrate the brain in a precisely controlled fashion. The resistance of the brain tissue being penetrated is continually monitored by a miniaturized strain gauge attached to the probe tip. Other modality sensors may be mounted near the probe tip to provide real-time tissue characterizations and the ability to detect the proximity of blood vessels, thus eliminating errors normally associated with registration of pre-operative scans, tissue swelling, elastic tissue deformation, human judgement, etc., and rendering surgical procedures safer, more accurate, and efficient. A neural network, program adaptively learns the information on resistance and other characteristic features of normal brain tissue during the surgery and provides near real-time modeling. A fuzzy logic interface to the neural network program incorporates expert medical knowledge in the learning process. Identification of abnormal brain tissue is determined by the detection of change and comparison with previously learned models of abnormal brain tissues. The operation of the instrument is controlled through a user friendly graphical interface. Patient data is presented in a 3D stereographics display. Acoustic feedback of selected information may optionally be provided. Upon detection of the close proximity to blood vessels or abnormal brain tissue, the computer-controlled motor immediately stops probe penetration.

The evolutionarily conserved G protein-coupled receptor SREB2/GPR85 influences brain size, behavior, and vulnerability to schizophrenia.

PubMed

Matsumoto, Mitsuyuki; Straub, Richard E; Marenco, Stefano; Nicodemus, Kristin K; Matsumoto, Shun-Ichiro; Fujikawa, Akihiko; Miyoshi, Sosuke; Shobo, Miwako; Takahashi, Shinji; Yarimizu, Junko; Yuri, Masatoshi; Hiramoto, Masashi; Morita, Shuji; Yokota, Hiroyuki; Sasayama, Takeshi; Terai, Kazuhiro; Yoshino, Masayasu; Miyake, Akira; Callicott, Joseph H; Egan, Michael F; Meyer-Lindenberg, Andreas; Kempf, Lucas; Honea, Robyn; Vakkalanka, Radha Krishna; Takasaki, Jun; Kamohara, Masazumi; Soga, Takatoshi; Hiyama, Hideki; Ishii, Hiroyuki; Matsuo, Ayako; Nishimura, Shintaro; Matsuoka, Nobuya; Kobori, Masato; Matsushime, Hitoshi; Katoh, Masao; Furuichi, Kiyoshi; Weinberger, Daniel R

2008-04-22

The G protein-coupled receptor (GPCR) family is highly diversified and involved in many forms of information processing. SREB2 (GPR85) is the most conserved GPCR throughout vertebrate evolution and is expressed abundantly in brain structures exhibiting high levels of plasticity, e.g., the hippocampal dentate gyrus. Here, we show that SREB2 is involved in determining brain size, modulating diverse behaviors, and potentially in vulnerability to schizophrenia. Mild overexpression of SREB2 caused significant brain weight reduction and ventricular enlargement in transgenic (Tg) mice as well as behavioral abnormalities mirroring psychiatric disorders, e.g., decreased social interaction, abnormal sensorimotor gating, and impaired memory. SREB2 KO mice showed a reciprocal phenotype, a significant increase in brain weight accompanying a trend toward enhanced memory without apparent other behavioral abnormalities. In both Tg and KO mice, no gross malformation of brain structures was observed. Because of phenotypic overlap between SREB2 Tg mice and schizophrenia, we sought a possible link between the two. Minor alleles of two SREB2 SNPs, located in intron 2 and in the 3' UTR, were overtransmitted to schizophrenia patients in a family-based sample and showed an allele load association with reduced hippocampal gray matter volume in patients. Our data implicate SREB2 as a potential risk factor for psychiatric disorders and its pathway as a target for psychiatric therapy.

Abnormal brain structure implicated in stimulant drug addiction.

PubMed

Ersche, Karen D; Jones, P Simon; Williams, Guy B; Turton, Abigail J; Robbins, Trevor W; Bullmore, Edward T

2012-02-03

Addiction to drugs is a major contemporary public health issue, characterized by maladaptive behavior to obtain and consume an increasing amount of drugs at the expense of the individual's health and social and personal life. We discovered abnormalities in fronto-striatal brain systems implicated in self-control in both stimulant-dependent individuals and their biological siblings who have no history of chronic drug abuse; these findings support the idea of an underlying neurocognitive endophenotype for stimulant drug addiction.

Fish consumption and risk of subclinical brain abnormalities on MRI in older adults.

PubMed

Virtanen, J K; Siscovick, D S; Longstreth, W T; Kuller, L H; Mozaffarian, D

2008-08-05

To investigate the association between fish consumption and subclinical brain abnormalities. In the population-based Cardiovascular Health Study, 3,660 participants age > or =65 underwent an MRI scan in 1992-1994. Five years later, 2,313 were scanned. Neuroradiologists assessed MRI scans in a standardized and blinded manner. Food frequency questionnaires were used to assess dietary intakes. Participants with known cerebrovascular disease were excluded from the analyses. After adjustment for multiple risk factors, the risk of having one or more prevalent subclinical infarcts was lower among those consuming tuna/other fish > or =3 times/week, compared to <1/month (relative risk 0.74, 95% CI = 0.54-1.01, p = 0.06, p trend = 0.03). Tuna/other fish consumption was also associated with trends toward lower incidence of subclinical infarcts. Additionally, tuna/other fish intake was associated with better white matter grade, but not with sulcal and ventricular grades, markers of brain atrophy. No significant associations were found between fried fish consumption and any subclinical brain abnormalities. Among older adults, modest consumption of tuna/other fish, but not fried fish, was associated with lower prevalence of subclinical infarcts and white matter abnormalities on MRI examinations. Our results add to prior evidence that suggest that dietary intake of fish with higher eicosapentaenoic acid and docosahexaenoic acid content, and not fried fish intake, may have clinically important health benefits.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism.

PubMed

Ritz, Ludivine; Segobin, Shailendra; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène; Pitel, Anne L

2016-09-01

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez's circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and (18)F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez's circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez's circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms. © The Author(s) 2015.

Direct voxel-based comparisons between grey matter shrinkage and glucose hypometabolism in chronic alcoholism

PubMed Central

Ritz, Ludivine; Segobin, Shailendra; Lannuzel, Coralie; Boudehent, Céline; Vabret, François; Eustache, Francis; Beaunieux, Hélène

2015-01-01

Alcoholism is associated with widespread brain structural abnormalities affecting mainly the frontocerebellar and the Papez’s circuits. Brain glucose metabolism has received limited attention, and few studies used regions of interest approach and showed reduced global brain metabolism predominantly in the frontal and parietal lobes. Even though these studies have examined the relationship between grey matter shrinkage and hypometabolism, none has performed a direct voxel-by-voxel comparison between the degrees of structural and metabolic abnormalities. Seventeen alcoholic patients and 16 control subjects underwent both structural magnetic resonance imaging and 18F-2-fluoro-deoxy-glucose-positron emission tomography examinations. Structural abnormalities and hypometabolism were examined in alcoholic patients compared with control subjects using two-sample t-tests. Then, these two patterns of brain damage were directly compared with a paired t-test. Compared to controls, alcoholic patients had grey matter shrinkage and hypometabolism in the fronto-cerebellar circuit and several nodes of Papez’s circuit. The direct comparison revealed greater shrinkage than hypometabolism in the cerebellum, cingulate cortex, thalamus and hippocampus and parahippocampal gyrus. Conversely, hypometabolism was more severe than shrinkage in the dorsolateral, premotor and parietal cortices. The distinct profiles of abnormalities found within the Papez’s circuit, the fronto-cerebellar circuit and the parietal gyrus in chronic alcoholism suggest the involvement of different pathological mechanisms. PMID:26661206

Impaired pitch perception and memory in congenital amusia: the deficit starts in the auditory cortex.

PubMed

Albouy, Philippe; Mattout, Jérémie; Bouet, Romain; Maby, Emmanuel; Sanchez, Gaëtan; Aguera, Pierre-Emmanuel; Daligault, Sébastien; Delpuech, Claude; Bertrand, Olivier; Caclin, Anne; Tillmann, Barbara

2013-05-01

Congenital amusia is a lifelong disorder of music perception and production. The present study investigated the cerebral bases of impaired pitch perception and memory in congenital amusia using behavioural measures, magnetoencephalography and voxel-based morphometry. Congenital amusics and matched control subjects performed two melodic tasks (a melodic contour task and an easier transposition task); they had to indicate whether sequences of six tones (presented in pairs) were the same or different. Behavioural data indicated that in comparison with control participants, amusics' short-term memory was impaired for the melodic contour task, but not for the transposition task. The major finding was that pitch processing and short-term memory deficits can be traced down to amusics' early brain responses during encoding of the melodic information. Temporal and frontal generators of the N100m evoked by each note of the melody were abnormally recruited in the amusic brain. Dynamic causal modelling of the N100m further revealed decreased intrinsic connectivity in both auditory cortices, increased lateral connectivity between auditory cortices as well as a decreased right fronto-temporal backward connectivity in amusics relative to control subjects. Abnormal functioning of this fronto-temporal network was also shown during the retention interval and the retrieval of melodic information. In particular, induced gamma oscillations in right frontal areas were decreased in amusics during the retention interval. Using voxel-based morphometry, we confirmed morphological brain anomalies in terms of white and grey matter concentration in the right inferior frontal gyrus and the right superior temporal gyrus in the amusic brain. The convergence between functional and structural brain differences strengthens the hypothesis of abnormalities in the fronto-temporal pathway of the amusic brain. Our data provide first evidence of altered functioning of the auditory cortices during pitch perception and memory in congenital amusia. They further support the hypothesis that in neurodevelopmental disorders impacting high-level functions (here musical abilities), abnormalities in cerebral processing can be observed in early brain responses.

Syndromic craniosynostosis: neuropsycholinguistic abilities and imaging analysis of the central nervous system.

PubMed

Maximino, Luciana Paula; Ducati, Luis Gustavo; Abramides, Dagma Venturini Marques; Corrêa, Camila de Castro; Garcia, Patrícia Fernandes; Fernandes, Adriano Yacubian

2017-12-01

To characterize patients with syndromic craniosynostosis with respect to their neuropsycholinguistic abilities and to present these findings together with the brain abnormalities. Eighteen patients with a diagnosis of syndromic craniosynostosis were studied. Eight patients had Apert syndrome and 10 had Crouzon syndrome. They were submitted to phonological evaluation, neuropsychological evaluation and magnetic resonance imaging of the brain. The phonological evaluation was done by behavioral observation of the language, the Peabody test, Token test and a school achievement test. The neuropsychological evaluation included the WISC III and WAIS tests. Abnormalities in language abilities were observed and the school achievement test showed abnormalities in 66.67% of the patients. A normal intelligence quotient was observed in 39.3% of the patients, and congenital abnormalities of the central nervous system were observed in 46.4% of the patients. Abnormalities of language abilities were observed in the majority of patients with syndromic craniosynostosis, and low cognitive performance was also observed.

Prenatal and Neonatal Brain Structure and White Matter Maturation in Children at High Risk for Schizophrenia

PubMed Central

Gilmore, John H.; Kang, Chaeryon; Evans, Dianne D.; Wolfe, Honor M.; Smith, J. Keith; Lieberman, Jeffrey A.; Lin, Weili; Hamer, Robert M.; Styner, Martin; Gerig, Guido

2011-01-01

Objective Schizophrenia is a neurodevelopmental disorder associated with abnormalities of brain structure and white matter, although little is known about when these abnormalities arise. This study was conducted to identify structural brain abnormalities in the prenatal and neonatal periods associated with genetic risk for schizophrenia. Method Prenatal ultrasound scans and neonatal structural magnetic resonance imaging (MRI) and diffusion tensor imaging were prospectively obtained in the offspring of mothers with schizophrenia or schizoaffective disorder (N=26) and matched comparison mothers without psychiatric illness (N=26). Comparisons were made for prenatal lateral ventricle width and head circumference, for neonatal intracranial, CSF, gray matter, white matter, and lateral ventricle volumes, and for neonatal diffusion properties of the genu and splenium of the corpus callosum and corticospinal tracts. Results Relative to the matched comparison subjects, the offspring of mothers with schizophrenia did not differ in prenatal lateral ventricle width or head circumference. Overall, the high-risk neonates had nonsignificantly larger intracranial, CSF, and lateral ventricle volumes. Subgroup analysis revealed that male high-risk infants had significantly larger intracranial, CSF, total gray matter, and lateral ventricle volumes; the female high-risk neonates were similar to the female comparison subjects. There were no group differences in white matter diffusion tensor properties. Conclusions Male neonates at genetic risk for schizophrenia had several larger than normal brain volumes, while females did not. To the authors' knowledge, this study provides the first evidence, in the context of its limitations, that early neonatal brain development may be abnormal in males at genetic risk for schizophrenia. PMID:20516153

The impact of substance use on brain structure in people at high risk of developing schizophrenia.

PubMed

Welch, Killian A; McIntosh, Andrew M; Job, Dominic E; Whalley, Heather C; Moorhead, Thomas W; Hall, Jeremy; Owens, David G C; Lawrie, Stephen M; Johnstone, Eve C

2011-09-01

Ventricular enlargement and reduced prefrontal volume are consistent findings in schizophrenia. Both are present in first episode subjects and may be detectable before the onset of clinical disorder. Substance misuse is more common in people with schizophrenia and is associated with similar brain abnormalities. We employ a prospective cohort study with nested case control comparison design to investigate the association between substance misuse, brain abnormality, and subsequent schizophrenia. Substance misuse history, imaging data, and clinical information were collected on 147 subjects at high risk of schizophrenia and 36 controls. Regions exhibiting a significant relationship between level of use of alcohol, cannabis or tobacco, and structure volume were identified. Multivariate regression then elucidated the relationship between level of substance use and structure volumes while accounting for correlations between these variables and correcting for potential confounders. Finally, we established whether substance misuse was associated with later risk of schizophrenia. Increased ventricular volume was associated with alcohol and cannabis use in a dose-dependent manner. Alcohol consumption was associated with reduced frontal lobe volume. Multiple regression analyses found both alcohol and cannabis were significant predictors of these abnormalities when simultaneously entered into the statistical model. Alcohol and cannabis misuse were associated with an increased subsequent risk of schizophrenia. We provide prospective evidence that use of cannabis or alcohol by people at high genetic risk of schizophrenia is associated with brain abnormalities and later risk of psychosis. A family history of schizophrenia may render the brain particularly sensitive to the risk-modifying effects of these substances.

Viral neurotropism, peripheral neuropathy and other morphological abnormalities in bovine ephemeral fever virus-infected downer cattle.

PubMed

Barigye, R; Davis, S; Hunt, R; Hunt, N; Walsh, S; Elliott, N; Burnup, C; Aumann, S; Day, C; Dyrting, K; Weir, R; Melville, L F

2016-10-01

This study assessed the neurotropism of bovine ephemeral fever (BEF) virus (BEFV) and described histomorphological abnormalities of the brain, spinal cord and peripheral nerves that may causally contribute to paresis or paralysis in BEF. Four paralysed and six asymptomatic but virus-infected cattle were monitored, and blood and serum samples screened by qRT-PCR, virus isolation and neutralisation tests. Fresh brain, spinal cord, peripheral nerve and other tissues were qRT-PCR-tested for viral RNA, while formalin-fixed specimens were processed routinely and immunohistochemically evaluated for histomorphological abnormalities and viral antigen distribution, respectively. The neurotropism of BEFV was immunohistochemically confirmed in the brain and peripheral nerves and peripheral neuropathy was demonstrated in three paralysed but not the six aneurological but virus-infected animals. Wallerian degeneration (WD) was present in the ventral funicular white matter of the lumbar spinal cord of a paralysed steer and in cervical and thoracic spinal cord segments of three paralysed animals. Although no spinal cord lesions were seen in the steer euthanased within 7 days of illness, peripheral neuropathy was present and more severe in nerves of the brachial plexuses than in the gluteal or fibular nerves. The only steer with WD in the lumbar spinal cord also showed intrahistiocytic cell viral antigen that was spatially distributed within areas of moderate brain stem encephalitis. The data confirmed neurotropism of BEFV in cattle and documented histomorphological abnormalities in peripheral nerves and brain which, together with spinal cord lesions, may contribute to chronic paralysis in BEFV-infected downer cattle. © 2016 Australian Veterinary Association.

Alterations in Brain Structure and Functional Connectivity in Alcohol Dependent Patients and Possible Association with Impulsivity.

PubMed

Wang, Junkai; Fan, Yunli; Dong, Yue; Ma, Mengying; Ma, Yi; Dong, Yuru; Niu, Yajuan; Jiang, Yin; Wang, Hong; Wang, Zhiyan; Wu, Liuzhen; Sun, Hongqiang; Cui, Cailian

2016-01-01

Previous studies have documented that heightened impulsivity likely contributes to the development and maintenance of alcohol use disorders. However, there is still a lack of studies that comprehensively detected the brain changes associated with abnormal impulsivity in alcohol addicts. This study was designed to investigate the alterations in brain structure and functional connectivity associated with abnormal impulsivity in alcohol dependent patients. Brain structural and functional magnetic resonance imaging data as well as impulsive behavior data were collected from 20 alcohol dependent patients and 20 age- and sex-matched healthy controls respectively. Voxel-based morphometry was used to investigate the differences of grey matter volume, and tract-based spatial statistics was used to detect abnormal white matter regions between alcohol dependent patients and healthy controls. The alterations in resting-state functional connectivity in alcohol dependent patients were examined using selected brain areas with gray matter deficits as seed regions. Compared with healthy controls, alcohol dependent patients had significantly reduced gray matter volume in the mesocorticolimbic system including the dorsal posterior cingulate cortex, the dorsal anterior cingulate cortex, the medial prefrontal cortex, the orbitofrontal cortex and the putamen, decreased fractional anisotropy in the regions connecting the damaged grey matter areas driven by higher radial diffusivity value in the same areas and decreased resting-state functional connectivity within the reward network. Moreover, the gray matter volume of the left medial prefrontal cortex exhibited negative correlations with various impulse indices. These findings suggest that chronic alcohol dependence could cause a complex neural changes linked to abnormal impulsivity.

Cortical venous disease severity in MELAS syndrome correlates with brain lesion development.

PubMed

Whitehead, M T; Wien, M; Lee, B; Bass, N; Gropman, A

2017-08-01

MELAS syndrome is a mitochondrial disorder typified by recurrent stroke-like episodes, seizures, and progressive brain injury. Abnormal mitochondria have been found in arterial walls implicating a vasculogenic etiology. We have observed abnormal cortical vein T2/FLAIR signal in MELAS patients, potentially representing wall thickening and sluggish flow. We sought to examine the relationship of hyperintense veins and brain lesions in MELAS. Imaging databases at two children's hospitals were searched for brain MRIs from MELAS patients. Artifact, sedated exams, and lack of 2D-T2/FLAIR sequences were exclusion criteria. Each exam was assigned a venous score based on number of T2/FLAIR hyperintense veins: 1 = <10, 2 = 10 to 20, 3 = >20. Cumulative brain lesions and venous score in MELAS and aged-matched normal exams were compared by Mann-Whitney test. A total of 106 exams from 14 unique MELAS patients (mean 16 ± 3 years) and 30 exams from normal aged-matched patients (mean 15 ± 3 years) were evaluated. Median venous score between MELAS and control patients significantly differed (3 versus 1; p < 0.001). In the MELAS group, venous score correlated with presence (median = 3) or absence (median = 1) of cumulative brain lesions. In all 8 MELAS patients who developed lesions, venous hyperintensity was present prior to, during, and after lesion onset. Venous score did not correlate with brain lesion acuity. Abnormal venous signal correlates with cumulative brain lesion severity in MELAS syndrome. Cortical venous stenosis, congestion, and venous ischemia may be mechanisms of brain injury. Identification of cortical venous pathology may aid in diagnosis and could be predictive of lesion development.

Comparison of O-(2-18F-Fluoroethyl)-L-Tyrosine Positron Emission Tomography and Perfusion-Weighted Magnetic Resonance Imaging in the Diagnosis of Patients with Progressive and Recurrent Glioma: A Hybrid Positron Emission Tomography/Magnetic Resonance Study.

PubMed

Verger, Antoine; Filss, Christian P; Lohmann, Philipp; Stoffels, Gabriele; Sabel, Michael; Wittsack, Hans-J; Kops, Elena Rota; Galldiks, Norbert; Fink, Gereon R; Shah, Nadim J; Langen, Karl-Josef

2018-05-01

To compare the diagnostic performance of O-(2- 18 F-fluoroethyl)-L-tyrosine ( 18 F-FET) positron emission tomography (PET) and perfusion-weighted magnetic resonance imaging (PWI) for the diagnosis of progressive or recurrent glioma. Thirty-two pretreated gliomas (25 progressive or recurrent tumors, 7 treatment-related changes) were investigated with 18 F-FET PET and PWI via a hybrid PET/magnetic resonance scanner. Volumes of interest with a diameter of 16 mm were centered on the maximum of abnormality in the tumor area in PET and PWI maps (relative cerebral blood volume, relative cerebral blood flow, mean transit time) and the contralateral unaffected hemisphere. Mean and maximum tumor-to-brain ratios as well as dynamic data for 18 F-FET uptake were calculated. Diagnostic accuracies were evaluated by receiver operating characteristic analyses, calculating the area under the curve. 18 F-FET PET showed a significant greater sensitivity to detect abnormalities in pretreated gliomas than PWI (76% vs. 52%, P = 0.03). The maximum tumor-to-brain ratio of 18 F-FET PET was the only parameter that discriminated treatment-related changes from progressive or recurrent gliomas (area under the curve, 0.78; P = 0.03, best cut-off 2.61; sensitivity 80%, specificity 86%, accuracy 81%). Among patients with signal abnormality in both modalities, 75% revealed spatially incongruent local hot spots. This pilot study suggests that 18 F-FET PET is superior to PWI to diagnose progressive or recurrent glioma. Copyright © 2018 Elsevier Inc. All rights reserved.

Abnormal subcortical nuclei shapes in patients with type 2 diabetes mellitus.

PubMed

Chen, Ji; Zhang, Junxiang; Liu, Xuebing; Wang, Xiaoyang; Xu, Xiangjin; Li, Hui; Cao, Bo; Yang, Yanqiu; Lu, Jingjing; Chen, Ziqian

2017-10-01

Type 2 diabetes mellitus (T2DM) increases the risk of brain atrophy and dementia. We aimed to elucidate deep grey matter (GM) structural abnormalities and their relationships with T2DM cognitive deficits by combining region of interest (ROI)-based volumetry, voxel-based morphometry (VBM) and shape analysis. We recruited 23 T2DM patients and 24 age-matched healthy controls to undergo T1-weighted structural MRI scanning. Images were analysed using the three aforementioned methods to obtain deep GM structural shapes and volumes. Biochemical and cognitive assessments were made and were correlated with the resulting metrics. Shape analysis revealed that T2DM is associated with focal atrophy in the bilateral caudate head and dorso-medial part of the thalamus. ROI-based volumetry only detected thalamic volume reduction in T2DM when compared to the controls. No significant between-group differences were found by VBM. Furthermore, a worse performance of cognitive processing speed correlated with more severe GM atrophy in the bilateral dorso-medial part of the thalamus. Also, the GM volume in the bilateral dorso-medial part of the thalamus changed negatively with HbA 1c . Shape analysis is sensitive in identifying T2DM deep GM structural abnormalities and their relationships with cognitive impairments, which may greatly assist in clarifying the neural substrate of T2DM cognitive dysfunction. • Type 2 diabetes mellitus is accompanied with brain atrophy and cognitive dysfunction • Deep grey matter structures are essential for multiple cognitive processes • Shape analysis revealed local atrophy in the dorso-medial thalamus and caudatum in patients • Dorso-medial thalamic atrophy correlated to cognitive processing speed slowing and high HbA1c. • Shape analysis has advantages in unraveling neural substrates of diabetic cognitive deficits.

Brain state-dependent abnormal LFP activity in the auditory cortex of a schizophrenia mouse model

PubMed Central

Nakao, Kazuhito; Nakazawa, Kazu

2014-01-01

In schizophrenia, evoked 40-Hz auditory steady-state responses (ASSRs) are impaired, which reflects the sensory deficits in this disorder, and baseline spontaneous oscillatory activity also appears to be abnormal. It has been debated whether the evoked ASSR impairments are due to the possible increase in baseline power. GABAergic interneuron-specific NMDA receptor (NMDAR) hypofunction mutant mice mimic some behavioral and pathophysiological aspects of schizophrenia. To determine the presence and extent of sensory deficits in these mutant mice, we recorded spontaneous local field potential (LFP) activity and its click-train evoked ASSRs from primary auditory cortex of awake, head-restrained mice. Baseline spontaneous LFP power in the pre-stimulus period before application of the first click trains was augmented at a wide range of frequencies. However, when repetitive ASSR stimuli were presented every 20 s, averaged spontaneous LFP power amplitudes during the inter-ASSR stimulus intervals in the mutant mice became indistinguishable from the levels of control mice. Nonetheless, the evoked 40-Hz ASSR power and their phase locking to click trains were robustly impaired in the mutants, although the evoked 20-Hz ASSRs were also somewhat diminished. These results suggested that NMDAR hypofunction in cortical GABAergic neurons confers two brain state-dependent LFP abnormalities in the auditory cortex; (1) a broadband increase in spontaneous LFP power in the absence of external inputs, and (2) a robust deficit in the evoked ASSR power and its phase-locking despite of normal baseline LFP power magnitude during the repetitive auditory stimuli. The “paradoxically” high spontaneous LFP activity of the primary auditory cortex in the absence of external stimuli may possibly contribute to the emergence of schizophrenia-related aberrant auditory perception. PMID:25018691

Increased frequency of brain pathology in inmates of a high-security forensic institution: a qualitative CT and MRI scan study.

PubMed

Witzel, Joachim G; Bogerts, Bernhard; Schiltz, Kolja

2016-09-01

This study aimed to assess whether brain pathology might be more abundant in forensic inpatients in a high-security setting than in non-criminal individuals. By using a previously used reliable approach, we explored the frequency and extent of brain pathology in a large group of institutionalized offenders who had not previously been considered to be suffering from structural brain damage and compare it to healthy, non-offending subjects. MRI and CT brain scans from 148 male inpatients of a high-security mental health institution (offense type: 51 sex, 80 violent, 9 arson, and 8 nonviolent) that were obtained due to headache, vertigo, or psychological complaints during imprisonment were assessed and compared to 52 non-criminal healthy controls. Brain scans were assessed qualitatively with respect to evidence of structural brain damage. Each case received a semiquantitative rating of "normal" (=0), "questionably abnormal" (=1), or "definitely abnormal" (=2) for the lateral ventricles, frontal/parietal cortex, and medial temporal structures bilaterally as well as third ventricle. Forensic inpatients displayed signs of brain damage to a significantly higher degree than healthy controls (p < 0.001). Even after adjustment for age, in the patients, being younger than the controls (p < 0.05), every offender type group displayed a higher proportion of subjects with brain regions categorized as definitely abnormal than the non-criminal controls. Within the forensic inpatients, offense type groups did not significantly differ in brain pathology. The astonishingly high prevalence of brain pathology in institutionalized inmates of a high-security mental health institution who previously had not been considered to be suffering from an organic brain syndrome raises questions on whether such neuroradiological assessment might be considered as a routine procedure in newly admitted patients. Furthermore, it highlights that organic changes, detectable under clinical routine conditions, may play a role in the development of legally relevant behavioral disturbances which might be underestimated.

Longitudinal tau PET in ageing and Alzheimer’s disease

PubMed Central

Jack, Clifford R; Wiste, Heather J; Schwarz, Christopher G; Lowe, Val J; Senjem, Matthew L; Vemuri, Prashanthi; Weigand, Stephen D; Therneau, Terry M; Knopman, Dave S; Gunter, Jeffrey L; Jones, David T; Graff-Radford, Jonathan; Kantarci, Kejal; Roberts, Rosebud O; Mielke, Michelle M; Machulda, Mary M; Petersen, Ronald C

2018-01-01

Abstract See Hansson and Mormino (doi:10.1093/brain/awy065) for a scientific commentary on this article. Our objective was to compare different whole-brain and region-specific measurements of within-person change on serial tau PET and evaluate its utility for clinical trials. We studied 126 individuals: 59 cognitively unimpaired with normal amyloid, 37 cognitively unimpaired with abnormal amyloid, and 30 cognitively impaired with an amnestic phenotype and abnormal amyloid. All had baseline amyloid PET and two tau PET, MRI, and clinical assessments. We compared the topography across all cortical regions of interest of tau PET accumulation rates and the rates of four different whole-brain or region-specific meta-regions of interest among the three clinical groups. We computed sample size estimates for change in tau PET, cortical volume, and memory/mental status indices for use as outcome measures in clinical trials. The cognitively unimpaired normal amyloid group had no observable tau accumulation throughout the brain. Tau accumulation rates in cognitively unimpaired abnormal amyloid were low [0.006 standardized uptake value ratio (SUVR), 0.5%, per year] but greater than rates in the cognitively unimpaired normal amyloid group in the basal and mid-temporal, retrosplenial, posterior cingulate, and entorhinal regions of interest. Thus, the earliest elevation in accumulation rates was widespread and not confined to the entorhinal cortex. Tau accumulation rates in the cognitively impaired abnormal amyloid group were 0.053 SUVR (3%) per year and greater than rates in cognitively unimpaired abnormal amyloid in all cortical areas except medial temporal. Rates of accumulation in the four meta-regions of interest differed but only slightly from one another. Among all tau PET meta-regions of interest, sample size estimates were smallest for a temporal lobe composite within cognitively unimpaired abnormal amyloid and for the late Alzheimer’s disease meta-region of interest within cognitively impaired abnormal amyloid. The ordering of the sample size estimates by outcome measure was MRI < tau PET < cognitive measures. At a group-wise level, observable rates of short-term serial tau accumulation were only seen in the presence of abnormal amyloid. As disease progressed to clinically symptomatic stages (cognitively impaired abnormal amyloid), observable rates of tau accumulation were seen uniformly throughout the brain providing evidence that tau does not accumulate in one area at a time or in start-stop, stepwise sequence. The information captured by rate measures in different meta-regions of interest, even those with little topographic overlap, was similar. The implication is that rate measurements from simple meta-regions of interest, without the need for Braak-like staging, may be sufficient to capture progressive within-person accumulation of pathologic tau. Tau PET SUVR measures should be an efficient outcome measure in disease-modifying clinical trials. PMID:29538647

Plasma serotonin in autism.

PubMed

Connors, Susan L; Matteson, Karla J; Sega, Gary A; Lozzio, Carmen B; Carroll, Roger C; Zimmerman, Andrew W

2006-09-01

Serotonin is necessary for normal fetal brain development. Administration of serotonin inhibitors to pregnant rats results in offspring with abnormal behaviors, brain morphology, and serotonin receptor numbers. Low maternal plasma serotonin may contribute to abnormal brain development in autism. In this study, plasma serotonin levels in autism mothers and control mothers of typically developing children were compared, and plasma serotonin levels in children with autism (n = 17) and their family members were measured. Plasma serotonin levels in autism mothers were significantly lower than in mothers of normal children (P = 0.002). Plasma serotonin levels correlated between autism mothers and their children, but differed between autistic children and their fathers (P = 0.028) and siblings (P = 0.063). Low maternal plasma serotonin may be a risk factor for autism through effects on fetal brain development.

High Incidence of Progressive Postnatal Cerebellar Enlargement in Costello Syndrome: Brain Overgrowth Associated with HRAS Mutations as the Likely Cause of Structural Brain and Spinal Cord Abnormalities

PubMed Central

Gripp, Karen W.; Hopkins, Elisabeth; Doyle, Daniel; Dobyns, William B.

2010-01-01

Costello syndrome is a rasopathy caused by germline mutations in the proto-oncogene HRAS. Its presentation includes failure-to-thrive with macrocephaly, characteristic facial features, hypertrophic cardiomyopathy, papillomata, malignant tumors, and cognitive impairment. In a systematic review we found absolute or relative macrocephaly (100%), ventriculomegaly (50%), and other abnormalities on brain and spinal cord imaging studies in 27/28 individuals. Posterior fossa crowding with cerebellar tonsillar herniation (CBTH) was noted in 27/28 (96%), and in 10/17 (59%) with serial studies posterior fossa crowding progressed. Sequelae of posterior fossa crowding and CBTH included hydrocephalus requiring shunt or ventriculostomy (25%), Chiari 1 malformation (32%) and syrinx formation (25%). Our data reveal macrocephaly with progressive frontal bossing and CBTH, documenting an ongoing process rather than a static congenital anomaly. Comparison of images obtained in young infants to subsequent studies demonstrated postnatal development of posterior fossa crowding. This process of evolving megalencephaly and cerebellar enlargement is in keeping with mouse model data, delineating abnormal genesis of neurons and glia, resulting in an increased number of astrocytes and enlarged brain volume. In Costello syndrome and macrocephaly-capillary malformation syndrome disproportionate brain growth is the main factor resulting in postnatal CBTH and Chiari 1 malformation. PMID:20425820

Establishing Mouse Models for Zika Virus-induced Neurological Disorders Using Intracerebral Injection Strategies: Embryonic, Neonatal, and Adult.

PubMed

Herrlinger, Stephanie A; Shao, Qiang; Ma, Li; Brindley, Melinda; Chen, Jian-Fu

2018-04-26

The Zika virus (ZIKV) is a flavivirus currently endemic in North, Central, and South America. It is now established that the ZIKV can cause microcephaly and additional brain abnormalities. However, the mechanism underlying the pathogenesis of ZIKV in the developing brain remains unclear. Intracerebral surgical methods are frequently used in neuroscience research to address questions about both normal and abnormal brain development and brain function. This protocol utilizes classical surgical techniques and describes methods that allow one to model ZIKV-associated human neurological disease in the mouse nervous system. While direct brain inoculation does not model the normal mode of virus transmission, the method allows investigators to ask targeted questions concerning the consequence after ZIKV infection of the developing brain. This protocol describes embryonic, neonatal, and adult stages of intraventricular inoculation of ZIKV. Once mastered, this method can become a straightforward and reproducible technique that only takes a few hours to perform.

Abnormal functional connectivity during visuospatial processing is associated with disrupted organisation of white matter in autism

PubMed Central

McGrath, Jane; Johnson, Katherine; O'Hanlon, Erik; Garavan, Hugh; Leemans, Alexander; Gallagher, Louise

2013-01-01

Disruption of structural and functional neural connectivity has been widely reported in Autism Spectrum Disorder (ASD) but there is a striking lack of research attempting to integrate analysis of functional and structural connectivity in the same study population, an approach that may provide key insights into the specific neurobiological underpinnings of altered functional connectivity in autism. The aims of this study were (1) to determine whether functional connectivity abnormalities were associated with structural abnormalities of white matter (WM) in ASD and (2) to examine the relationships between aberrant neural connectivity and behavior in ASD. Twenty-two individuals with ASD and 22 age, IQ-matched controls completed a high-angular-resolution diffusion MRI scan. Structural connectivity was analysed using constrained spherical deconvolution (CSD) based tractography. Regions for tractography were generated from the results of a previous study, in which 10 pairs of brain regions showed abnormal functional connectivity during visuospatial processing in ASD. WM tracts directly connected 5 of the 10 region pairs that showed abnormal functional connectivity; linking a region in the left occipital lobe (left BA19) and five paired regions: left caudate head, left caudate body, left uncus, left thalamus, and left cuneus. Measures of WM microstructural organization were extracted from these tracts. Fractional anisotropy (FA) reductions in the ASD group relative to controls were significant for WM connecting left BA19 to left caudate head and left BA19 to left thalamus. Using a multimodal imaging approach, this study has revealed aberrant WM microstructure in tracts that directly connect brain regions that are abnormally functionally connected in ASD. These results provide novel evidence to suggest that structural brain pathology may contribute (1) to abnormal functional connectivity and (2) to atypical visuospatial processing in ASD. PMID:24133425

Rivastigmine

MedlinePlus

... in people with Parkinson's disease (a brain and nervous system disease with symptoms of slowing of movement, muscle ... develops abnormal protein structures, and the brain and nervous system are destroyed over time). Talk to your doctor ...

Astrocytes.

ERIC Educational Resources Information Center

Kimelberg, Harold K.; Norenberg, Michael D.

1989-01-01

Describes the astrocytes' function as equal partners with neurons in both the normal and the abnormal brain. Discusses the developmental scaffolds, inert scar tissue, Huntington's disease, psychiatric disorders, and the identification of these brain cells. (RT)

Diffusion tensor imaging and myelin composition analysis reveal abnormal myelination in corpus callosum of canine mucopolysaccharidosis I

PubMed Central

Provenzale, James M.; Nestrasil, Igor; Chen, Steven; Kan, Shih-hsin; Le, Steven Q.; Jens, Jacqueline K.; Snella, Elizabeth M.; Vondrak, Kristen N.; Yee, Jennifer K.; Vite, Charles H.; Elashoff, David; Duan, Lewei; Wang, Raymond Y.; Ellinwood, N. Matthew; Guzman, Miguel A.; Shapiro, Elsa G.; Dickson, Patricia I.

2015-01-01

Children with mucopolysaccharidosis I (MPS I) develop hyperintense white matter foci on T2-weighted brain magnetic resonance (MR) imaging that are associated clinically with cognitive impairment. We report here a diffusion tensor imaging (DTI) and tissue evaluation of white matter in a canine model of MPS I. We found that two DTI parameters, fractional anisotropy (a measure of white matter integrity) and radial diffusivity (which reflects degree of myelination) were abnormal in the corpus callosum of MPS I dogs compared to carrier controls. Tissue studies of the corpus callosum showed reduced expression of myelin-related genes and an abnormal composition of myelin in MPS I dogs. We treated MPS I dogs with recombinant alpha-l-iduronidase, which is the enzyme that is deficient in MPS I disease. The recombinant alpha-l-iduronidase was administered by intrathecal injection into the cisterna magna. Treated dogs showed partial correction of corpus callosum myelination. Our findings suggest that abnormal myelination occurs in the canine MPS I brain, that it may underlie clinically-relevant brain imaging findings in human MPS I patients, and that it may respond to treatment. PMID:26222335

Neuroimaging markers of glutamatergic and GABAergic systems in drug addiction: Relationships to resting-state functional connectivity.

PubMed

Moeller, Scott J; London, Edythe D; Northoff, Georg

2016-02-01

Drug addiction is characterized by widespread abnormalities in brain function and neurochemistry, including drug-associated effects on concentrations of the excitatory and inhibitory neurotransmitters glutamate and gamma-aminobutyric acid (GABA), respectively. In healthy individuals, these neurotransmitters drive the resting state, a default condition of brain function also disrupted in addiction. Here, our primary goal was to review in vivo magnetic resonance spectroscopy and positron emission tomography studies that examined markers of glutamate and GABA abnormalities in human drug addiction. Addicted individuals tended to show decreases in these markers compared with healthy controls, but findings also varied by individual characteristics (e.g., abstinence length). Interestingly, select corticolimbic brain regions showing glutamatergic and/or GABAergic abnormalities have been similarly implicated in resting-state functional connectivity deficits in drug addiction. Thus, our secondary goals were to provide a brief review of this resting-state literature, and an initial rationale for the hypothesis that abnormalities in glutamatergic and/or GABAergic neurotransmission may underlie resting-state functional deficits in drug addiction. In doing so, we suggest future research directions and possible treatment implications. Copyright © 2015 Elsevier Ltd. All rights reserved.

Automatic Seizure Detection Based on Morphological Features Using One-Dimensional Local Binary Pattern on Long-Term EEG.

PubMed

Shanir, P P Muhammed; Khan, Kashif Ahmad; Khan, Yusuf Uzzaman; Farooq, Omar; Adeli, Hojjat

2017-12-01

Epileptic neurological disorder of the brain is widely diagnosed using the electroencephalography (EEG) technique. EEG signals are nonstationary in nature and show abnormal neural activity during the ictal period. Seizures can be identified by analyzing and obtaining features of EEG signal that can detect these abnormal activities. The present work proposes a novel morphological feature extraction technique based on the local binary pattern (LBP) operator. LBP provides a unique decimal value to a sample point by weighing the binary outcomes after thresholding the neighboring samples with the present sample point. These LBP values assist in capturing the rising and falling edges of the EEG signal, thus providing a morphologically featured discriminating pattern for epilepsy detection. In the present work, the variability in the LBP values is measured by calculating the sum of absolute difference of the consecutive LBP values. Interquartile range is calculated over the preprocessed EEG signal to provide dispersion measure in the signal. For classification purpose, K-nearest neighbor classifier is used, and the performance is evaluated on 896.9 hours of data from CHB-MIT continuous EEG database. Mean accuracy of 99.7% and mean specificity of 99.8% is obtained with average false detection rate of 0.47/h and sensitivity of 99.2% for 136 seizures.

Combat veterans with PTSD after mild TBI exhibit greater ERPs from posterior-medial cortical areas while appraising facial features.

PubMed

Shu, I-Wei; Onton, Julie A; Prabhakar, Nitin; O'Connell, Ryan M; Simmons, Alan N; Matthews, Scott C

2014-02-01

Posttraumatic stress disorder (PTSD) worsens prognosis following mild traumatic brain injury (mTBI). Combat personnel with histories of mTBI exhibit abnormal activation of distributed brain networks-including emotion processing and default mode networks. How developing PTSD further affects these abnormalities has not been directly examined. We recorded electroencephalography in combat veterans with histories of mTBI, but without active PTSD (mTBI only, n=16) and combat veterans who developed PTSD after mTBI (mTBI+PTSD, n=16)-during the Reading the Mind in the Eyes Test (RMET), a validated test of empathy requiring emotional appraisal of facial features. Task-related event related potentials (ERPs) were identified, decomposed using independent component analysis (ICA) and localized anatomically using dipole modeling. We observed larger emotional face processing ERPs in veterans with mTBI+PTSD, including greater N300 negativity. Furthermore, greater N300 negativity correlated with greater PTSD severity, especially avoidance/numbing and hyperarousal symptom clusters. This correlation was dependent on contributions from the precuneus and posterior cingulate cortex (PCC). Our results support a model where, in combat veterans with histories of mTBI, larger ERPs from over-active posterior-medial cortical areas may be specific to PTSD, and is likely related to negative self-referential activity. © 2013 Published by Elsevier B.V.

Grey Matter Alterations Co-Localize with Functional Abnormalities in Developmental Dyslexia: An ALE Meta-Analysis

PubMed Central

Linkersdörfer, Janosch; Lonnemann, Jan; Lindberg, Sven; Hasselhorn, Marcus; Fiebach, Christian J.

2012-01-01

The neural correlates of developmental dyslexia have been investigated intensively over the last two decades and reliable evidence for a dysfunction of left-hemispheric reading systems in dyslexic readers has been found in functional neuroimaging studies. In addition, structural imaging studies using voxel-based morphometry (VBM) demonstrated grey matter reductions in dyslexics in several brain regions. To objectively assess the consistency of these findings, we performed activation likelihood estimation (ALE) meta-analysis on nine published VBM studies reporting 62 foci of grey matter reduction in dyslexic readers. We found six significant clusters of convergence in bilateral temporo-parietal and left occipito-temporal cortical regions and in the cerebellum bilaterally. To identify possible overlaps between structural and functional deviations in dyslexic readers, we conducted additional ALE meta-analyses of imaging studies reporting functional underactivations (125 foci from 24 studies) or overactivations (95 foci from 11 studies ) in dyslexics. Subsequent conjunction analyses revealed overlaps between the results of the VBM meta-analysis and the meta-analysis of functional underactivations in the fusiform and supramarginal gyri of the left hemisphere. An overlap between VBM results and the meta-analysis of functional overactivations was found in the left cerebellum. The results of our study provide evidence for consistent grey matter variations bilaterally in the dyslexic brain and substantial overlap of these structural variations with functional abnormalities in left hemispheric regions. PMID:22916214

Local corticotropin releasing hormone (CRH) signals to its receptor CRHR1 during postnatal development of the mouse olfactory bulb.

PubMed

Garcia, Isabella; Bhullar, Paramjit K; Tepe, Burak; Ortiz-Guzman, Joshua; Huang, Longwen; Herman, Alexander M; Chaboub, Lesley; Deneen, Benjamin; Justice, Nicholas J; Arenkiel, Benjamin R

2016-01-01

Neuropeptides play important physiological functions during distinct behaviors such as arousal, learning, memory, and reproduction. However, the role of local, extrahypothalamic neuropeptide signaling in shaping synapse formation and neuronal plasticity in the brain is not well understood. Here, we characterize the spatiotemporal expression profile of the neuropeptide corticotropin-releasing hormone (CRH) and its receptor CRHR1 in the mouse OB throughout development. We found that CRH-expressing interneurons are present in the external plexiform layer, that its cognate receptor is expressed by granule cells, and show that both CRH and CRHR1 expression enriches in the postnatal period when olfaction becomes important towards olfactory-related behaviors. Further, we provide electrophysiological evidence that CRHR1-expressing granule cells functionally respond to CRH ligand, and that the physiological circuitry of CRHR1 knockout mice is abnormal, leading to impaired olfactory behaviors. Together, these data suggest a physiologically relevant role for local CRH signaling towards shaping the neuronal circuitry within the mouse OB.

Medication Overuse Headache: Pathophysiological Insights from Structural and Functional Brain MRI Research.

PubMed

Schwedt, Todd J; Chong, Catherine D

2017-07-01

Research imaging of brain structure and function has helped to elucidate the pathophysiology of medication overuse headache (MOH). This is a narrative review of imaging research studies that have investigated brain structural and functional alterations associated with MOH. Studies included in this review have investigated abnormal structure and function of pain processing regions in people with MOH, functional patterns that might predispose individuals to development of MOH, similarity of brain functional patterns in patients with MOH to those found in people with addiction, brain structure that could predict headache improvement following discontinuation of the overused medication, and changes in brain structure and function after discontinuation of medication overuse. MOH is associated with atypical structure and function of brain regions responsible for pain processing as well as brain regions that are commonly implicated in addiction. Several studies have shown "normalization" of structure and function in pain processing regions following discontinuation of the overused medication and resolution of MOH. However, some of the abnormalities in regions also implicated in addiction tend to persist following discontinuation of the overused medication, suggesting that they are a brain trait that predisposes certain individuals to medication overuse and MOH. © 2017 American Headache Society.

Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies

PubMed Central

Edland, Steven D.; Hemmy, Laura S.; Montine, Kathleen S.; Zarow, Chris; Sonnen, Joshua A.; Uyehara-Lock, Jane H.; Gelber, Rebecca P.; Ross, G. Webster; Petrovitch, Helen; Masaki, Kamal H.; Lim, Kelvin O.; Launer, Lenore J.; Montine, Thomas J.

2016-01-01

Objective: To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. Methods: The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. Results: Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. Conclusions: Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life. PMID:26888993

Neuropathologic comorbidity and cognitive impairment in the Nun and Honolulu-Asia Aging Studies.

PubMed

White, Lon R; Edland, Steven D; Hemmy, Laura S; Montine, Kathleen S; Zarow, Chris; Sonnen, Joshua A; Uyehara-Lock, Jane H; Gelber, Rebecca P; Ross, G Webster; Petrovitch, Helen; Masaki, Kamal H; Lim, Kelvin O; Launer, Lenore J; Montine, Thomas J

2016-03-15

To examine frequencies and relationships of 5 common neuropathologic abnormalities identified at autopsy with late-life cognitive impairment and dementia in 2 different autopsy panels. The Nun Study (NS) and the Honolulu-Asia Aging Study (HAAS) are population-based investigations of brain aging that included repeated cognitive assessments and comprehensive brain autopsies. The neuropathologic abnormalities assessed were Alzheimer disease (AD) neuropathologic changes, neocortical Lewy bodies (LBs), hippocampal sclerosis, microinfarcts, and low brain weight. Associations with screening tests for cognitive impairment were examined. Neuropathologic abnormalities occurred at levels ranging from 9.7% to 43%, and were independently associated with cognitive impairment in both studies. Neocortical LBs and AD changes were more frequent among the predominantly Caucasian NS women, while microinfarcts were more common in the Japanese American HAAS men. Comorbidity was usual and very strongly associated with cognitive impairment. Apparent cognitive resilience (no cognitive impairment despite Braak stage V) was strongly associated with minimal or no comorbid abnormalities, with fewer neocortical AD lesions, and weakly with longer interval between final testing and autopsy. Total burden of comorbid neuropathologic abnormalities, rather than any single lesion type, was the most relevant determinant of cognitive impairment in both cohorts, often despite clinical diagnosis of only AD. These findings emphasize challenges to dementia pathogenesis and intervention research and to accurate diagnoses during life. © 2016 American Academy of Neurology.

Developing Gene Silencing for the Study and Treatment of Dystonia

DTIC Science & Technology

2016-10-01

eliminate the symptoms? Are the motor deficits in DYT1 dystonia reversible? We propose to use a novel rat model of DYT1 dystonia and infuse antisense...suppressing expression of mutant torsinA in striatum or cerebellum using AAV1 reverses the motor phenotype in aged DYT1 rats . 4. IMPACT What was...different areas of the brain, and w e w ill measure if they are able to reverse known abnormalities that occur in the brain of DYT1 rats , including abnormal

Microvascular and Macrovascular Abnormalities and Cognitive and Physical Function in Older Adults: Cardiovascular Health Study.

PubMed

Kim, Dae Hyun; Grodstein, Francine; Newman, Anne B; Chaves, Paulo H M; Odden, Michelle C; Klein, Ronald; Sarnak, Mark J; Lipsitz, Lewis A

2015-09-01

To evaluate and compare the associations between microvascular and macrovascular abnormalities and cognitive and physical function Cross-sectional analysis of the Cardiovascular Health Study (1998-1999). Community. Individuals with available data on three or more of five microvascular abnormalities (brain, retina, kidney) and three or more of six macrovascular abnormalities (brain, carotid artery, heart, peripheral artery) (N = 2,452; mean age 79.5). Standardized composite scores derived from three cognitive tests (Modified Mini-Mental State Examination, Digit-Symbol Substitution Test, Trail-Making Test (TMT)) and three physical tests (gait speed, grip strength, 5-time sit to stand) Participants with high microvascular and macrovascular burden had worse cognitive (mean score difference = -0.30, 95% confidence interval (CI) = -0.37 to -0.24) and physical (mean score difference = -0.32, 95% CI = -0.38 to -0.26) function than those with low microvascular and macrovascular burden. Individuals with high microvascular burden alone had similarly lower scores than those with high macrovascular burden alone (cognitive function: -0.16, 95% CI = -0.24 to -0.08 vs -0.13, 95% CI = -0.20 to -0.06; physical function: -0.15, 95% CI = -0.22 to -0.08 vs -0.12, 95% CI = -0.18 to -0.06). Psychomotor speed and working memory, assessed using the TMT, were only impaired in the presence of high microvascular burden. Of the 11 vascular abnormalities considered, white matter hyperintensity, cystatin C-based glomerular filtration rate, large brain infarct, and ankle-arm index were independently associated with cognitive and physical function. Microvascular and macrovascular abnormalities assessed using noninvasive tests of the brain, kidney, and peripheral artery were independently associated with poor cognitive and physical function in older adults. Future research should evaluate the usefulness of these tests in prognostication. © 2015, Copyright the Authors Journal compilation © 2015, The American Geriatrics Society.

North Carolina Genomic Evaluation by Next-generation Exome Sequencing, 2

ClinicalTrials.gov

2018-06-06

Epilepsy; Seizure; Neuromuscular Diseases; Brain Malformation; Intellectual Disability; Autism Spectrum Disorder; Hypotonia; Inborn Errors of Metabolism; Movement Disorders; Genetic Disease; Development Delay; Chromosome Abnormality; Hearing Loss; Dysmorphic Features; Skeletal Dysplasia; Congenital Abnormality; Microcephaly; Macrocephaly

The role of tau in the pathological process and clinical expression of Huntington’s disease

PubMed Central

Vuono, Romina; Winder-Rhodes, Sophie; de Silva, Rohan; Cisbani, Giulia; Drouin-Ouellet, Janelle; Spillantini, Maria G.; Cicchetti, Francesca

2015-01-01

Huntington’s disease is a neurodegenerative disorder caused by an abnormal CAG repeat expansion within exon 1 of the huntingtin gene HTT. While several genetic modifiers, distinct from the Huntington’s disease locus itself, have been identified as being linked to the clinical expression and progression of Huntington’s disease, the exact molecular mechanisms driving its pathogenic cascade and clinical features, especially the dementia, are not fully understood. Recently the microtubule associated protein tau, MAPT, which is associated with several neurodegenerative disorders, has been implicated in Huntington’s disease. We explored this association in more detail at the neuropathological, genetic and clinical level. We first investigated tau pathology by looking for the presence of hyperphosphorylated tau aggregates, co-localization of tau with mutant HTT and its oligomeric intermediates in post-mortem brain samples from patients with Huntington’s disease (n = 16) compared to cases with a known tauopathy and healthy controls. Next, we undertook a genotype–phenotype analysis of a large cohort of patients with Huntington’s disease (n = 960) with a particular focus on cognitive decline. We report not only on the tau pathology in the Huntington’s disease brain but also the association between genetic variation in tau gene and the clinical expression and progression of the disease. We found extensive pathological inclusions containing abnormally phosphorylated tau protein that co-localized in some instances with mutant HTT. We confirmed this related to the disease process rather than age, by showing it is also present in two patients with young-onset Huntington’s disease (26 and 40 years old at death). In addition we demonstrate that tau oligomers (suggested to be the most likely neurotoxic tau entity) are present in the Huntington’s disease brains. Finally we highlight the clinical significance of this pathology by demonstrating that the MAPT haplotypes affect the rate of cognitive decline in a large cohort of patients with Huntington’s disease. Our findings therefore highlight a novel important role of tau in the pathogenic process and clinical expression of Huntington’s disease, which in turn opens up new therapeutic avenues for this incurable condition. PMID:25953777

Developmental abnormalities and age-related neurodegeneration in a mouse model of Down syndrome

PubMed Central

Holtzman, David M.; Santucci, Daniela; Kilbridge, Joshua; Chua-Couzens, Jane; Fontana, David J.; Daniels, Scott E.; Johnson, Randolph M.; Chen, Karen; Sun, Yuling; Carlson, Elaine; Alleva, Enrico; Epstein, Charles J.; Mobley, William C.

1996-01-01

To study the pathogenesis of central nervous system abnormalities in Down syndrome (DS), we have analyzed a new genetic model of DS, the partial trisomy 16 (Ts65Dn) mouse. Ts65Dn mice have an extra copy of the distal aspect of mouse chromosome 16, a segment homologous to human chromosome 21 that contains much of the genetic material responsible for the DS phenotype. Ts65Dn mice show developmental delay during the postnatal period as well as abnormal behaviors in both young and adult animals that may be analogous to mental retardation. Though the Ts65Dn brain is normal on gross examination, there is age-related degeneration of septohippocampal cholinergic neurons and astrocytic hypertrophy, markers of the Alzheimer disease pathology that is present in elderly DS individuals. These findings suggest that Ts65Dn mice may be used to study certain developmental and degenerative abnormalities in the DS brain. PMID:8917591

Region-specific protein misfolding cyclic amplification reproduces brain tropism of prion strains.

PubMed

Privat, Nicolas; Levavasseur, Etienne; Yildirim, Serfildan; Hannaoui, Samia; Brandel, Jean-Philippe; Laplanche, Jean-Louis; Béringue, Vincent; Seilhean, Danielle; Haïk, Stéphane

2017-10-06

Human prion diseases such as Creutzfeldt-Jakob disease are transmissible brain proteinopathies, characterized by the accumulation of a misfolded isoform of the host cellular prion protein (PrP) in the brain. According to the prion model, prions are defined as proteinaceous infectious particles composed solely of this abnormal isoform of PrP (PrP Sc ). Even in the absence of genetic material, various prion strains can be propagated in experimental models. They can be distinguished by the pattern of disease they produce and especially by the localization of PrP Sc deposits within the brain and the spongiform lesions they induce. The mechanisms involved in this strain-specific targeting of distinct brain regions still are a fundamental, unresolved question in prion research. To address this question, we exploited a prion conversion in vitro assay, protein misfolding cyclic amplification (PMCA), by using experimental scrapie and human prion strains as seeds and specific brain regions from mice and humans as substrates. We show here that region-specific PMCA in part reproduces the specific brain targeting observed in experimental, acquired, and sporadic Creutzfeldt-Jakob diseases. Furthermore, we provide evidence that, in addition to cellular prion protein, other region- and species-specific molecular factors influence the strain-dependent prion conversion process. This important step toward understanding prion strain propagation in the human brain may impact research on the molecular factors involved in protein misfolding and the development of ultrasensitive methods for diagnosing prion disease. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

How to Link Brain and Experience? Spatiotemporal Psychopathology of the Lived Body

PubMed Central

Northoff, Georg; Stanghellini, Giovanni

2016-01-01

The focus of the present article is on sketching a psychopathology of the body in schizophrenia and linking it to brain activity. This is done providing converging data from psychopathological evidence (phenomenal), phenomenological contructs (trans-phenomenal) and neuroscientific measures (pre-phenomenal). The phenomenal level is the detailed documentation of the patients’ subjective anomalous experiences. These phenomena are explicit contents in the patients’ field of consciousness. The trans-phenomenal level targets the implicit yet operative matrix that underlies these anomalous subjective experiences. Abnormal phenomena are viewed as expressions of a modification of trans-phenomenal matrix, that is, in terms of an abnormal synthesis or integration through time of intero-, proprio- and extero-ceptive stimuli. Finally, we link the abnormalities of the trans-phenomenal matrix to pre-phenomenal alterations of the brain resting state and of its spatio-temporal organization, as documented by neurobiological methods providing spatial and temporal resolution of intrinsic brain activity (with many features of the resting state remaining yet unclear though). Based on phenomenological research, the body in schizophrenia is typically experienced in an itemized way as an object external to one’s self and unrelated to events in the external world. Based on neurobiological data, we tentatively hypothesize that such anomalies of the lived body are related to decreased integration between intero-, extero- and proprioceptive experiences by the brain’s spontaneous activity and its temporal structure. Taken all together, this suggests that we view abnormalities of bodily experience in terms of their underlying abnormal spatiotemporal features which, as we suppose, can be traced back to the spatiotemporal features of the brain’s spontaneous activity. PMID:27199695

Simulation of realistic abnormal SPECT brain perfusion images: application in semi-quantitative analysis

NASA Astrophysics Data System (ADS)

Ward, T.; Fleming, J. S.; Hoffmann, S. M. A.; Kemp, P. M.

2005-11-01

Simulation is useful in the validation of functional image analysis methods, particularly when considering the number of analysis techniques currently available lacking thorough validation. Problems exist with current simulation methods due to long run times or unrealistic results making it problematic to generate complete datasets. A method is presented for simulating known abnormalities within normal brain SPECT images using a measured point spread function (PSF), and incorporating a stereotactic atlas of the brain for anatomical positioning. This allows for the simulation of realistic images through the use of prior information regarding disease progression. SPECT images of cerebral perfusion have been generated consisting of a control database and a group of simulated abnormal subjects that are to be used in a UK audit of analysis methods. The abnormality is defined in the stereotactic space, then transformed to the individual subject space, convolved with a measured PSF and removed from the normal subject image. The dataset was analysed using SPM99 (Wellcome Department of Imaging Neuroscience, University College, London) and the MarsBaR volume of interest (VOI) analysis toolbox. The results were evaluated by comparison with the known ground truth. The analysis showed improvement when using a smoothing kernel equal to system resolution over the slightly larger kernel used routinely. Significant correlation was found between effective volume of a simulated abnormality and the detected size using SPM99. Improvements in VOI analysis sensitivity were found when using the region median over the region mean. The method and dataset provide an efficient methodology for use in the comparison and cross validation of semi-quantitative analysis methods in brain SPECT, and allow the optimization of analysis parameters.

Cognition and brain development in children with benign epilepsy with centrotemporal spikes.

PubMed

Garcia-Ramos, Camille; Jackson, Daren C; Lin, Jack J; Dabbs, Kevin; Jones, Jana E; Hsu, David A; Stafstrom, Carl E; Zawadzki, Lucy; Seidenberg, Michael; Prabhakaran, Vivek; Hermann, Bruce P

2015-10-01

Benign epilepsy with centrotemporal spikes (BECTS), the most common focal childhood epilepsy, is associated with subtle abnormalities in cognition and possible developmental alterations in brain structure when compared to healthy participants, as indicated by previous cross-sectional studies. To examine the natural history of BECTS, we investigated cognition, cortical thickness, and subcortical volumes in children with new/recent onset BECTS and healthy controls (HC). Participants were 8-15 years of age, including 24 children with new-onset BECTS and 41 age- and gender-matched HC. At baseline and 2 years later, all participants completed a cognitive assessment, and a subset (13 BECTS, 24 HC) underwent T1 volumetric magnetic resonance imaging (MRI) scans focusing on cortical thickness and subcortical volumes. Baseline cognitive abnormalities associated with BECTS (object naming, verbal learning, arithmetic computation, and psychomotor speed/dexterity) persisted over 2 years, with the rate of cognitive development paralleling that of HC. Baseline neuroimaging revealed thinner cortex in BECTS compared to controls in frontal, temporal, and occipital regions. Longitudinally, HC showed widespread cortical thinning in both hemispheres, whereas BECTS participants showed sparse regions of both cortical thinning and thickening. Analyses of subcortical volumes showed larger left and right putamens persisting over 2 years in BECTS compared to HC. Cognitive and structural brain abnormalities associated with BECTS are present at onset and persist (cognition) and/or evolve (brain structure) over time. Atypical maturation of cortical thickness antecedent to BECTS onset results in early identified abnormalities that continue to develop abnormally over time. However, compared to anatomic development, cognition appears more resistant to further change over time. Wiley Periodicals, Inc. © 2015 International League Against Epilepsy.

Differential Hemispheric Predilection of Microstructural White Matter and Functional Connectivity Abnormalities between Respectively Semantic and Behavioral Variant Frontotemporal Dementia.

PubMed

Meijboom, Rozanna; Steketee, Rebecca M E; Ham, Leontine S; van der Lugt, Aad; van Swieten, John C; Smits, Marion

2017-01-01

Semantic dementia (SD) and behavioral variant frontotemporal dementia (bvFTD), subtypes of frontotemporal dementia, are characterized by distinct clinical symptoms and neuroimaging features, with predominant left temporal grey matter (GM) atrophy in SD and bilateral or right frontal GM atrophy in bvFTD. Such differential hemispheric predilection may also be reflected by other neuroimaging features, such as brain connectivity. This study investigated white matter (WM) microstructure and functional connectivity differences between SD and bvFTD, focusing on the hemispheric predilection of these differences. Eight SD and 12 bvFTD patients, and 17 controls underwent diffusion tensor imaging and resting state functional MRI at 3T. Whole-brain WM microstructure was assessed to determine distinct WM tracts affected in SD and bvFTD. For these tracts, diffusivity measures and lateralization indices were calculated. Functional connectivity was established for GM regions affected in early stage SD or bvFTD. Results of a direct comparison between SD and bvFTD are reported. Whole-brain WM microstructure abnormalities were more pronounced in the left hemisphere in SD and bilaterally- with a slight predilection for the right- in bvFTD. Lateralization of tract-specific abnormalities was seen in SD only, toward the left hemisphere. Functional connectivity of disease-specific regions was mainly decreased bilaterally in SD and in the right hemisphere in bvFTD. SD and bvFTD show WM microstructure and functional connectivity abnormalities in different regions, that are respectively more pronounced in the left hemisphere in SD and in the right hemisphere in bvFTD. This indicates differential hemispheric predilection of brain connectivity abnormalities between SD and bvFTD.

Abnormal brain aging as a radical-related disease: A new target for nuclear medicine

DOE Office of Scientific and Technical Information (OSTI.GOV)

Fujibayashi, Y.; Yamamoto, S.; Waki, A.

DNA damages caused by endogenously produced radicals are closely correlated with aging. Among them, mitochondrial DNA (mtDNA) deletions have been reported as a memory of DNA damage by oxygen radicals. In fact, clinical as well as experimental studies indicated the accumulation of deleted mtDNA in the brain, myocardium and son on, in aged subjects. In our previous work, radioiodinated radical trapping agent, p-iodophenyl-N-t-butylnitrone, and hypoxia imaging agent, Cu-62 diacetyl-bis-N-4-methyl-thiosemicarbazone have been developed for the diagnosis of radical-related diseases, such as ischemic, inflammation, cancer or aging. The aim of the present work was to evaluate these agents for brain aging studies.more » In our university, an unique animal model, a senescence accelerated model mouse (SAM), has been established. Among the various substrains, SAMP8 showing memory deterioration in its young age ({approximately}3 month) was basically evaluated as an abnormal brain aging model with mtDNA deletion. As controls, SAMR1 showing normal aging and ddY mice were used. MtDNA deletion n the brain was analyzed with polymerase-chain reaction (PCR) method, and relationship between mtDNA deletion and brain uptake of IPBN or Cu-62-ATSM was studied. In 1-3 month old SAMP8 brain, multiple mtDNa deletions were already found and their content was significantly higher than that of SAMR1 or age-matched ddY control. Thus, it was cleared that SAMP8 brain has high tendency to be attacked by endogenously produced oxygen radicals, possibly from its birth. Both IPBN and Cu-ATSM showed significantly higher accumulation in the SAMP8 brain than in the SAMR1 brain, indicating that these agents have high possibility for the early detection of abnormal brain aging as a radical-related disease.« less

Progressive brain atrophy in patients with chronic neuropsychiatric symptoms after mild traumatic brain injury: a preliminary study.

PubMed

Ross, David E; Ochs, Alfred L; Seabaugh, Jan M; Demark, Michael F; Shrader, Carole R; Marwitz, Jennifer H; Havranek, Michael D

2012-01-01

NeuroQuant® is a recently developed, FDA-approved software program for measuring brain MRI volume in clinical settings. The aims of this study were as follows: (1) to examine the test-retest reliability of NeuroQuant®; (2) to test the hypothesis that patients with mild traumatic brain injury (TBI) would have abnormally rapid progressive brain atrophy; and (3) to test the hypothesis that progressive brain atrophy in patients with mild TBI would be associated with vocational outcome. Sixteen patients with mild TBI were compared to 20 normal controls. Vocational outcome was assessed with the Glasgow Outcome Scale-Extended (GOSE) and Disability Rating Scale (DRS). NeuroQuant® showed high test-re-test reliability. Patients had abnormally rapid progressive atrophy in several brain regions and the rate of atrophy was associated with inability to return to work. NeuroQuant®, is a reliable and valid method for assessing the anatomic effects of TBI. Progression of atrophy may continue for years after injury, even in patients with mild TBI.

Effects of hyperglycemia on fluorine-18-fluorodeoxyglucose biodistribution in a large oncology clinical practice.

PubMed

Rosica, Dillenia; Cheng, Su-Chun; Hudson, Margo; Sakellis, Christopher; Van den Abbeele, Annick D; Kim, Chun K; Jacene, Heather A

2018-05-01

Suggested cutoff points of blood glucose levels (BGL) before F-FDG PET/CT scanning vary between 120 and 200 mg/dl in current guidelines. This study's purpose was to compare the frequency of abnormal fluorine-18-fluorodeoxyglucose (F-FDG) biodistribution on PET/CT scans of patients with various ranges of abnormal BGL and to determine the effect of BGL greater than 200 mg/dl on F-FDG uptake in various organs. F-FDG PET/CT scans were retrospectively reviewed for 325 patients with BGL greater than 120 mg/dl at the time of scan and 112 with BGL less than or equal to 120 mg/dl. F-FDG biodistribution was categorized as normal, mildly abnormal, or abnormal by visual analysis of brain, background soft tissue, and muscle. Mean standardized uptake values (SUVmean) in brain, liver, fat (flank), gluteal muscle, and blood pool (aorta) were recorded. F-FDG biodistribution frequencies were assessed using a nonparametric χ-test for trend. Normal organ SUVs were compared using Kruskal-Wallis tests using the following BGL groupings: ≤120, 121-150, 151-200, and ≥201 mg/dl. Although higher BGL were significantly associated with an increased proportion of abnormal biodistribution (P<0.001), most patients with BGL less than or equal to 200 mg/dl had normal or mildly abnormal biodistribution. Average brain SUVmean significantly decreased with higher BGL groupings (P<0.001). Average aorta, gluteal muscle, and liver SUVmean did not significantly differ among groups with BGL greater than 120 mg/dl (P=0.66, 0.84, and 0.39, respectively), but were significantly lower in those with BGL less than or equal to 120 mg/dl (P≤0.001). Flank fat SUVmean was not significantly different among BGL groups (P=0.67). Abnormal F-FDG biodistribution is associated with higher BGL at the time of scan, but the effects are negligible or mild in most patients with BGL less than 200 mg/dl. Although mildly increased soft tissue uptake is seen with BGL greater than 120 mg/dl, decline in brain metabolic activity correlated the most with various BGL.

Imaging Alzheimer's disease pathophysiology with PET

PubMed Central

Schilling, Lucas Porcello; Zimmer, Eduardo R.; Shin, Monica; Leuzy, Antoine; Pascoal, Tharick A.; Benedet, Andréa L.; Borelli, Wyllians Vendramini; Palmini, André; Gauthier, Serge; Rosa-Neto, Pedro

2016-01-01

ABSTRACT Alzheimer's disease (AD) has been reconceptualised as a dynamic pathophysiological process characterized by preclinical, mild cognitive impairment (MCI), and dementia stages. Positron emission tomography (PET) associated with various molecular imaging agents reveals numerous aspects of dementia pathophysiology, such as brain amyloidosis, tau accumulation, neuroreceptor changes, metabolism abnormalities and neuroinflammation in dementia patients. In the context of a growing shift toward presymptomatic early diagnosis and disease-modifying interventions, PET molecular imaging agents provide an unprecedented means of quantifying the AD pathophysiological process, monitoring disease progression, ascertaining whether therapies engage their respective brain molecular targets, as well as quantifying pharmacological responses. In the present study, we highlight the most important contributions of PET in describing brain molecular abnormalities in AD. PMID:29213438

Hypopituitarism in pediatric survivors of inflicted traumatic brain injury.

PubMed

Auble, Bethany A; Bollepalli, Sureka; Makoroff, Kathi; Weis, Tammy; Khoury, Jane; Colliers, Tracy; Rose, Susan R

2014-02-15

Endocrine dysfunction is common after accidental traumatic brain injury (TBI). Prevalence of endocrine dysfunction after inflicted traumatic brain injury (iTBI) is not known. The aim of this study was to examine endocrinopathy in children after moderate-to-severe iTBI. Children with previous iTBI (n=14) were evaluated for growth/endocrine dysfunction, including anthropometric measurements and hormonal evaluation (nocturnal growth hormone [GH], thyrotropin surge, morning and low-dose adrenocorticotropin stimulated cortisol, insulin-like growth factor 1, IGF-binding protein 3, free thyroxine, prolactin [PRL], and serum/urine osmolality). Analysis used Fisher's exact test and Wilcoxon's rank-sum test, as appropriate. Eighty-six percent of subjects had endocrine dysfunction with at least one abnormality, whereas 50% had two or more abnormalities, significantly increased compared to an estimated 2.5% with endocrine abnormality in the general population (p<0.001). Elevated prolactin was common (64%), followed by abnormal thyroid function (33%), short stature (29%), and low GH peak (17%). High prolactin was common in subjects with other endocrine abnormalities. Two were treated with thyroid hormone and 2 may require GH therapy. In conclusion, children with a history of iTBI show high risk for endocrine dysfunction, including elevated PRL and growth abnormalities. This effect of iTBI has not been well described in the literature. Larger, multi-center, prospective studies would provide more data to determine the extent of endocrine dysfunction in iTBI. We recommend that any child with a history of iTBI be followed closely for growth velocity and pubertal changes. If growth velocity is slow, PRL level and a full endocrine evaluation should be performed.

Functional connectivity and microstructural white matter changes in phenocopy frontotemporal dementia.

PubMed

Meijboom, R; Steketee, R M E; de Koning, I; Osse, R J; Jiskoot, L C; de Jong, F J; van der Lugt, A; van Swieten, J C; Smits, M

2017-04-01

Phenocopy frontotemporal dementia (phFTD) is a rare and poorly understood clinical syndrome. PhFTD shows core behavioural variant FTD (bvFTD) symptoms without associated cognitive deficits and brain abnormalities on conventional MRI and without progression. In contrast to phFTD, functional connectivity and white matter (WM) microstructural abnormalities have been observed in bvFTD. We hypothesise that phFTD belongs to the same disease spectrum as bvFTD and investigated whether functional connectivity and microstructural WM changes similar to bvFTD are present in phFTD. Seven phFTD patients without progression or alternative psychiatric diagnosis, 12 bvFTD patients and 17 controls underwent resting state functional MRI (rs-fMRI) and diffusion tensor imaging (DTI). Default mode network (DMN) connectivity and WM measures were compared between groups. PhFTD showed subtly increased DMN connectivity and subtle microstructural changes in frontal WM tracts. BvFTD showed abnormalities in similar regions as phFTD, but had lower increased DMN connectivity and more extensive microstructural WM changes. Our findings can be interpreted as neuropathological changes in phFTD and are in support of the hypothesis that phFTD and bvFTD may belong to the same disease spectrum. Advanced MRI techniques, objectively identifying brain abnormalities, would therefore be potentially suited to improve the diagnosis of phFTD. • PhFTD shows brain abnormalities that are similar to bvFTD. • PhFTD shows increased functional connectivity in the parietal default mode network. • PhFTD shows microstructural white matter abnormalities in the frontal lobe. • We hypothesise phFTD and bvFTD may belong to the same disease spectrum.

Brain connectome modularity in weight-restored anorexia nervosa and body dysmorphic disorder

PubMed Central

Zhang, A; Leow, A; Zhan, L; GadElkarim, J; Moody, T; Khalsa, S; Strober, M; Feusner, JD

2017-01-01

Background Anorexia nervosa (AN) and body dysmorphic disorder (BDD) frequently co-occur, and have several overlapping phenomenological features. Little is known about their shared neurobiology. Aims To compare modular organization of brain structural connectivity. Methods We acquired diffusion-weighted magnetic resonance imaging data on unmedicated individuals with BDD (n=29), weight-restored AN (n=24), and healthy controls (HC) (n=31). We constructed connectivity matrices using whole-brain white matter tractography, and compared modular structures across groups. Results AN showed abnormal modularity involving frontal, basal ganglia, and posterior cingulate nodes. There was a trend in BDD for similar abnormalities, but no significant differences compared with AN. In AN, poor insight correlated with longer path length in right caudal anterior cingulate and right posterior cingulate. Conclusions Abnormal network organization patterns in AN, partially shared with BDD, may have implications for understanding integration between reward and habit/ritual formation, as well as conflict monitoring/error detection. PMID:27429183

Enhanced exosome secretion in Down syndrome brain - a protective mechanism to alleviate neuronal endosomal abnormalities.

PubMed

Gauthier, Sébastien A; Pérez-González, Rocío; Sharma, Ajay; Huang, Fang-Ke; Alldred, Melissa J; Pawlik, Monika; Kaur, Gurjinder; Ginsberg, Stephen D; Neubert, Thomas A; Levy, Efrat

2017-08-29

A dysfunctional endosomal pathway and abnormally enlarged early endosomes in neurons are an early characteristic of Down syndrome (DS) and Alzheimer's disease (AD). We have hypothesized that endosomal material can be released by endosomal multivesicular bodies (MVBs) into the extracellular space via exosomes to relieve neurons of accumulated endosomal contents when endosomal pathway function is compromised. Supporting this, we found that exosome secretion is enhanced in the brains of DS patients and a mouse model of the disease, and by DS fibroblasts. Furthermore, increased levels of the tetraspanin CD63, a regulator of exosome biogenesis, were observed in DS brains. Importantly, CD63 knockdown diminished exosome release and worsened endosomal pathology in DS fibroblasts. Taken together, these data suggest that increased CD63 expression enhances exosome release as an endogenous mechanism mitigating endosomal abnormalities in DS. Thus, the upregulation of exosome release represents a potential therapeutic goal for neurodegenerative disorders with endosomal pathology.

Neurodevelopment and executive function in autism.

PubMed

O'Hearn, Kirsten; Asato, Miya; Ordaz, Sarah; Luna, Beatriz

2008-01-01

Autism is a neurodevelopmental disorder characterized by social and communication deficits, and repetitive behavior. Studies investigating the integrity of brain systems in autism suggest a wide range of gray and white matter abnormalities that are present early in life and change with development. These abnormalities predominantly affect association areas and undermine functional integration. Executive function, which has a protracted development into adolescence and reflects the integration of complex widely distributed brain function, is also affected in autism. Evidence from studies probing response inhibition and working memory indicate impairments in these core components of executive function, as well as compensatory mechanisms that permit normative function in autism. Studies also demonstrate age-related improvements in executive function from childhood to adolescence in autism, indicating the presence of plasticity and suggesting a prolonged window for effective treatment. Despite developmental gains, mature executive functioning is limited in autism, reflecting abnormalities in wide-spread brain networks that may lead to impaired processing of complex information across all domains.

Seizures and electroencephalography findings in 61 patients with fetal alcohol spectrum disorders.

PubMed

Boronat, S; Vicente, M; Lainez, E; Sánchez-Montañez, A; Vázquez, E; Mangado, L; Martínez-Ribot, L; Del Campo, M

2017-01-01

Fetal alcohol spectrum disorders (FASD) cause neurodevelopmental abnormalities. However, publications about epilepsy and electroencephalographic features are scarce. In this study, we prospectively performed electroencephalography (EEG) and brain magnetic resonance (MR) imaging in 61 patients with diagnosis of FASD. One patient had multiple febrile seizures with normal EEGs. Fourteen children showed EEG anomalies, including slow background activity and interictal epileptiform discharges, focal and/or generalized, and 3 of them had epilepsy. In one patient, seizures were first detected during the EEG recording and one case had an encephalopathy with electrical status epilepticus during slow sleep (ESES). Focal interictal discharges in our patients did not imply the presence of underlying visible focal brain lesions in the neuroimaging studies, such as cortical dysplasia or polymicrogyria. However, they had nonspecific brain MR abnormalities, including corpus callosum hypoplasia, vermis hypoplasia or cavum septum pellucidum. The latter was significantly more frequent in the group with EEG abnormal findings (p < 0.01). Copyright © 2016 Elsevier Masson SAS. All rights reserved.

Distinct time courses of secondary brain damage in the hippocampus following brain concussion and contusion in rats.

PubMed

Nakajima, Yuko; Horiuchi, Yutaka; Kamata, Hiroshi; Yukawa, Masayoshi; Kuwabara, Masato; Tsubokawa, Takashi

2010-07-01

Secondary brain damage (SBD) is caused by apoptosis after traumatic brain injury that is classified into concussion and contusion. Brain concussion is temporary unconsciousness or confusion caused by a blow on the head without pathological changes, and contusion is a brain injury with hemorrhage and broad extravasations. In this study, we investigated the time-dependent changes of apoptosis in hippocampus after brain concussion and contusion using rat models. We generated the concussion by dropping a plumb on the dura from a height of 3.5 cm and the contusion by cauterizing the cerebral cortex. SBD was evaluated in the hippocampus by histopathological analyses and measuring caspase-3 activity that induces apoptotic neuronal cell death. The frequency of abnormal neuronal cells with vacuolation or nuclear condensation, or those with DNA fragmentation was remarkably increased at 1 hr after concussion (about 30% for each abnormality) from the pre-injury level (0%) and reached the highest level (about 50% for each) by 48 hrs, whereas the frequency of abnormal neuronal cells was increased at 1 hr after contusion (about 10%) and reached the highest level (about 40%) by 48 hrs. In parallel, caspase-3 activity was increased sevenfold in the hippocampus at 1 hr after concussion and returned to the pre-injury level by 48 hrs, whereas after contusion, caspase-3 activity was continuously increased to the highest level at 48 hrs (fivefold). Thus, anti-apoptotic-cell-death treatment to prevent SBD must be performed by 1 hr after concussion and at latest by 48 hrs after contusion.

Dermatoglyphics in relation to brain volumes in twins concordant and discordant for bipolar disorder.

PubMed

Vonk, R; van der Schot, A C; van Baal, G C M; van Oel, C J; Nolen, W A; Kahn, R S

2014-12-01

Palmar and finger dermatoglyphics are formed between the 10th and the 17th weeks of gestation and their morphology can be influenced by genetic or environmental factors, interfering with normal intrauterine development. As both the skin and the brain develop from the same embryonal ectoderm, dermatoglyphic alterations may be informative for early abnormal neurodevelopmental processes in the brain. We investigated whether dermatoglyphic alterations are related to structural brain abnormalities in bipolar disorder and to what extent they are of a genetic and of an environmental origin. Dermatoglyphics and volumetric data from structural MRI were obtained in 53 twin pairs concordant or discordant for bipolar disorder and 51 healthy matched control twin pairs. Structural equation modeling was used. Bipolar disorder was significantly positively associated with palmar a-b ridge count (ABRC), indicating higher ABRC in bipolar patients (rph=.17 (CI .04-.30)). Common genes appear to be involved because the genetic correlation with ABRC was significant (rph-A=.21 (CI .05-.36). Irrespective of disease, ABRC showed a genetically mediated association with brain volume, indicated by a significant genetic correlation rph-A of respectively -.36 (CI -.52 to -.22) for total brain, -.34 (CI -.51 to -.16) total cortical volume, -.27 (CI -.43 to -.08) cortical gray matter and -.23 (CI -.41 to -.04) cortical white matter. In conclusion, a genetically determined abnormal development of the foetal ectoderm between the 10th and 15th week of gestation appears related to smaller brain volumes in (subjects at risk for) bipolar disorder. Copyright © 2014 Elsevier B.V. and ECNP. All rights reserved.

Assessment of the usefulness of magnetic resonance brain imaging in patients presenting with acute seizures.

PubMed

Olszewska, D A; Costello, D J

2014-12-01

Magnetic Resonance Imaging (MRI) is increasingly available as a tool for assessment of patients presenting to acute services with seizures. We set out to prospectively determine the usefulness of early MRI brain in a cohort of patients presenting with acute seizures. We examined the MR imaging studies performed in patients admitted solely because of acute seizures to Cork University Hospital over a 12-month period. The main aim of the study was to determine if the MRI established the proximate cause for the patient's recent seizure. We identified 91 patients who underwent MRI brain within 48 h of admission for seizures. Of the 91 studies, 51 were normal (56 %). The remaining 40 studies were abnormal as follows: microvascular disease (usually moderate/severe) (n = 19), post-traumatic gliosis (n = 7), remote symptomatic lesion (n = 6), primary brain tumour (n = 5), venous sinus thrombosis (n = 3), developmental lesion (n = 3), post-surgical gliosis (n = 3) and single cases of demyelination, unilateral hippocampal sclerosis, lobar haemorrhage and metastatic malignant melanoma. Abnormalities in diffusion-weighted sequences that were attributable to prolonged ictal activity were seen in nine patients, all of who had significant ongoing clinical deficits, most commonly delirium. Of the 40 patients with abnormal MRI studies, seven patients had unremarkable CT brain. MR brain imaging revealed the underlying cause for acute seizures in 44 % of patients. CT brain imaging failed to detect the cause of the acute seizures in 19 % of patients in whom subsequent MRI established the cause. This study emphasises the importance of obtaining optimal imaging in people admitted with acute seizures.

Neonatal physiological correlates of near-term brain development on MRI and DTI in very-low-birth-weight preterm infants.

PubMed

Rose, Jessica; Vassar, Rachel; Cahill-Rowley, Katelyn; Stecher Guzman, Ximena; Hintz, Susan R; Stevenson, David K; Barnea-Goraly, Naama

2014-01-01

Structural brain abnormalities identified at near-term age have been recognized as potential predictors of neurodevelopment in children born preterm. The aim of this study was to examine the relationship between neonatal physiological risk factors and early brain structure in very-low-birth-weight (VLBW) preterm infants using structural MRI and diffusion tensor imaging (DTI) at near-term age. Structural brain MRI, diffusion-weighted scans, and neonatal physiological risk factors were analyzed in a cross-sectional sample of 102 VLBW preterm infants (BW ≤ 1500 g, gestational age (GA) ≤ 32 weeks), who were admitted to the Lucile Packard Children's Hospital, Stanford NICU and recruited to participate prior to routine near-term brain MRI conducted at 36.6 ± 1.8 weeks postmenstrual age (PMA) from 2010 to 2011; 66/102 also underwent a diffusion-weighted scan. Brain abnormalities were assessed qualitatively on structural MRI, and white matter (WM) microstructure was analyzed quantitatively on DTI in six subcortical regions defined by DiffeoMap neonatal brain atlas. Specific regions of interest included the genu and splenium of the corpus callosum, anterior and posterior limbs of the internal capsule, the thalamus, and the globus pallidus. Regional fractional anisotropy (FA) and mean diffusivity (MD) were calculated using DTI data and examined in relation to neonatal physiological risk factors including gestational age (GA), bronchopulmonary dysplasia (BPD), necrotizing enterocolitis (NEC), retinopathy of prematurity (ROP), and sepsis, as well as serum levels of C-reactive protein (CRP), glucose, albumin, and total bilirubin. Brain abnormalities were observed on structural MRI in 38/102 infants including 35% of females and 40% of males. Infants with brain abnormalities observed on MRI had higher incidence of BPD (42% vs. 25%) and sepsis (21% vs. 6%) and higher mean and peak serum CRP levels, respectively, (0.64 vs. 0.34 mg/dL, p = .008; 1.57 vs. 0.67 mg/dL, p= .006) compared to those without. The number of signal abnormalities observed on structural MRI correlated to mean and peak CRP (rho = .316, p = .002; rho = .318, p= .002). The number of signal abnormalities observed on MRI correlated with thalamus MD (left: r= .382, p= .002; right: r= .400, p= .001), controlling for PMA-at-scan. Thalamus WM microstructure demonstrated the strongest associations with neonatal risk factors. Higher thalamus MD on the left and right, respectively, was associated with lower GA (r = -.322, p = .009; r= -.381, p= .002), lower mean albumin (r = -.276, p= .029; r= -.385, p= .002), and lower mean bilirubin (r = -.293, p= .020; r= -.337 p= .007). Results suggest that at near-term age, thalamus WM microstructure may be particularly vulnerable to certain neonatal risk factors. Interactions between albumin, bilirubin, phototherapy, and brain development warrant further investigation. Identification of physiological risk factors associated with selective vulnerability of certain brain regions at near-term age may clarify the etiology of neurodevelopmental impairment and inform neuroprotective treatment for VLBW preterm infants.

L-threo-dihydroxyphenylserine corrects neurochemical abnormalities in a Menkes disease mouse model.

PubMed

Donsante, Anthony; Sullivan, Patricia; Goldstein, David S; Brinster, Lauren R; Kaler, Stephen G

2013-02-01

Menkes disease is a lethal neurodegenerative disorder of infancy caused by mutations in a copper-transporting adenosine triphosphatase gene, ATP7A. Among its multiple cellular tasks, ATP7A transfers copper to dopamine beta hydroxylase (DBH) within the lumen of the Golgi network or secretory granules, catalyzing the conversion of dopamine to norepinephrine. In a well-established mouse model of Menkes disease, mottled-brindled (mo-br), we tested whether systemic administration of L-threo-dihydroxyphenylserine (L-DOPS), a drug used successfully to treat autosomal recessive norepinephrine deficiency, would improve brain neurochemical abnormalities and neuropathology. At 8, 10, and 12 days of age, wild-type and mo-br mice received intraperitoneal injections of 200μg/g body weight of L-DOPS, or mock solution. Five hours after the final injection, the mice were euthanized, and brains were removed. We measured catecholamine metabolites affected by DBH via high-performance liquid chromatography with electrochemical detection, and assessed brain histopathology. Compared to mock-treated controls, mo-br mice that received intraperitoneal L-DOPS showed significant increases in brain norepinephrine (p < 0.001) and its deaminated metabolite, dihydroxyphenylglycol (p < 0.05). The ratio of a non-beta-hydroxylated metabolite in the catecholamine biosynthetic pathway, dihydroxyphenylacetic acid, to the beta-hydroxylated metabolite, dihydroxyphenylglycol, improved equivalently to results obtained previously with brain-directed ATP7A gene therapy (p < 0.01). However, L-DOPS treatment did not arrest global brain pathology or improve somatic growth, as gene therapy had. We conclude that (1) L-DOPS crosses the blood-brain barrier in mo-br mice and corrects brain neurochemical abnormalities, (2) norepinephrine deficiency is not the cause of neurodegeneration in mo-br mice, and (3) L-DOPS treatment may ameliorate noradrenergic hypofunction in Menkes disease. Copyright © 2012 American Neurological Association.

L-DOPS corrects neurochemical abnormalities in a Menkes disease mouse model

PubMed Central

Donsante, Anthony; Sullivan, Patricia; Goldstein, David S.; Brinster, Lauren R.; Kaler, Stephen G.

2012-01-01

Objective Menkes disease is a lethal neurodegenerative disorder of infancy caused by mutations in a copper-transporting ATPase gene, ATP7A. Among its multiple cellular tasks, ATP7A transfers copper to dopamine-beta-hydroxylase (DBH) within the lumen of the Golgi network or secretory granules, catalyzing the conversion of dopamine to norepinephrine. In a well-established mouse model of Menkes disease, mottled-brindled, we tested whether systemic administration of L-threo-dihydroxyphenylserine (L-DOPS), a drug used successfully to treat autosomal recessive norepinephrine deficiency, would improve brain neurochemical abnormalities and neuropathology. Methods At 8, 10, and 12 days of age, wild type and mo-br mice received intraperi-toneal injections of 200μg/g body weight of L-DOPS, or mock solution. Five hours after the final injection, the mice were euthanized and brains removed. We measured catecholamine metabolites affected by DBH via high-performance liquid chromatography with electrochemical detection, and assessed brain histopathology. Results Compared to mock-treated controls, mo-br mice that received intraperitoneal L-DOPS showed significant increases in brain norepinephrine (P<0.001) and its deaminated metabolite, dihydroxyphenylglycol (DHPG, P<0.05). The ratio of a non-beta-hydroxylated metabolite in the catecholamine biosynthetic pathway, dihydroxyphenylacetic acid, to the beta-hydroxylated metabolite, dihydroxyphenylglycol, improved equivalently to results obtained previously with brain-directed ATP7A gene therapy (P<0.01). However, L-DOPS treatment did not arrest global brain pathology or improve somatic growth, as gene therapy had. Interpretation We conclude that 1) L-DOPS crosses the blood-brain barrier in mo-br mice and corrects brain neurochemical abnormalities, 2) norepinephrine deficiency is not the cause of neurodegeneration in mo-br mice, and 3) L-DOPS treatment may ameliorate noradrenergic hypofunction in Menkes disease. PMID:23224983

Contribution of fetal brain MRI in management of severe fetal anemia.

PubMed

Ghesquière, L; Houfflin-Debarge, V; Verpillat, P; Fourquet, T; Joriot, S; Coulon, C; Vaast, P; Garabedian, C

2018-06-06

Intrauterine transfusion (IUT) has changed fetal anemia prognosis. However, long-term neurodevelopmental outcome is altered in 5% of children. Our objective was to study the contribution of fetal MRI to diagnosis brain lesions in case of fetal anemia. Retrospective monocentric descriptive study from 2005 to 2016, including all patients followed for fetal anemia requiring IUT. The indications for MRI were: hydrops fetalis and / or hemoglobin <5 g / dL and / or more than 3 IUTs and / or acute severe anemia and / or ultrasound abnormality. Fetal and neonatal outcome and pediatric neurological monitoring were studied. 89 patients were followed for fetal anemia with IUT and 28 (29.1%) had fetal MRI, 12 of which were abnormal. Two out of twelve had abnormal ultrasound. Seven out of twelve had poor neurological prognosis: 2 medical terminations of pregnancy were performed; 2 children had severe developmental delay and 3 children had schooling difficulties. Five out of twelve children had favorable neurological prognosis. MRI of the fetal brain makes it possible to better detect brain lesions than ultrasound does in the management of severe fetal anemia and seems particularly appropriate in cases of acute anemia. Copyright © 2018 Elsevier B.V. All rights reserved.

Dandy-Walker syndrome and chromosomal abnormalities.

PubMed

Imataka, George; Yamanouchi, Hideo; Arisaka, Osamu

2007-12-01

Dandy-Walker syndrome (DWS) is a brain malformation of unknown etiology, but several reports have been published indicating that there is a causal relationship to various types of chromosomal abnormalities and malformation syndromes. In the present article, we present a bibliographical survey of several previously issued reports on chromosomal abnormalities associated with DWS, including our case of DWS found in trisomy 18. There are various types of chromosomal abnormalities associated with DWS; most of them are reported in chromosome 3, 9, 13 and 18. We also summarize some other chromosomal abnormalities and various congenital malformation syndromes.

Fetal MRI: head and neck.

PubMed

Mirsky, David M; Shekdar, Karuna V; Bilaniuk, Larissa T

2012-08-01

Abnormalities of the fetal head and neck may be seen in isolation or in association with central nervous system abnormalities, chromosomal abnormalities, and syndromes. Magnetic resonance imaging (MRI) plays an important role in detecting associated abnormalities of the brain as well as in evaluating for airway obstruction that may impact prenatal management and delivery planning. This article provides an overview of the common indications for MRI of the fetal head and neck, including abnormalities of the fetal skull and face, masses of the face and neck, and fetal goiter. Copyright © 2012 Elsevier Inc. All rights reserved.

Disrupted topological organization in whole-brain functional networks of heroin-dependent individuals: a resting-state FMRI study.

PubMed

Jiang, Guihua; Wen, Xue; Qiu, Yingwei; Zhang, Ruibin; Wang, Junjing; Li, Meng; Ma, Xiaofen; Tian, Junzhang; Huang, Ruiwang

2013-01-01

Neuroimaging studies have shown that heroin addiction is related to abnormalities in widespread local regions and in the functional connectivity of the brain. However, little is known about whether heroin addiction changes the topological organization of whole-brain functional networks. Seventeen heroin-dependent individuals (HDIs) and 15 age-, gender-matched normal controls (NCs) were enrolled, and the resting-state functional magnetic resonance images (RS-fMRI) were acquired from these subjects. We constructed the brain functional networks of HDIs and NCs, and compared the between-group differences in network topological properties using graph theory method. We found that the HDIs showed decreases in the normalized clustering coefficient and in small-worldness compared to the NCs. Furthermore, the HDIs exhibited significantly decreased nodal centralities primarily in regions of cognitive control network, including the bilateral middle cingulate gyrus, left middle frontal gyrus, and right precuneus, but significantly increased nodal centralities primarily in the left hippocampus. The between-group differences in nodal centralities were not corrected by multiple comparisons suggesting these should be considered as an exploratory analysis. Moreover, nodal centralities in the left hippocampus were positively correlated with the duration of heroin addiction. Overall, our results indicated that disruptions occur in the whole-brain functional networks of HDIs, findings which may be helpful in further understanding the mechanisms underlying heroin addiction.

Spontaneous alterations of regional brain activity in patients with adult generalized anxiety disorder

PubMed Central

Xia, Likun; Li, Shumei; Wang, Tianyue; Guo, Yaping; Meng, Lihong; Feng, Yunping; Cui, Yu; Wang, Fan; Ma, Jian; Jiang, Guihua

2017-01-01

Objective We aimed to examine how spontaneous brain activity might be related to the pathophysiology of generalized anxiety disorder (GAD). Patients and methods Using resting-state functional MRI, we examined spontaneous regional brain activity in 31 GAD patients (mean age, 36.87±9.16 years) and 36 healthy control participants (mean age, 39.53±8.83 years) matched for age, education, and sex from December 2014 to October 2015. We performed a two-sample t-test on the voxel-based analysis of the regional homogeneity (ReHo) maps. We used Pearson correlation analysis to compare scores from the Hamilton Anxiety Rating Scale, Hamilton Depression Rating Scale, State–Trait Anxiety Scale-Trait Scale, and mean ReHo values. Results We found abnormal spontaneous activity in multiple regions of brain in GAD patients, especially in the sensorimotor cortex and emotional regions. GAD patients showed decreased ReHo values in the right orbital middle frontal gyrus, left anterior cingulate cortex, right middle frontal gyrus, and bilateral supplementary motor areas, with increased ReHo values in the left middle temporal gyrus, left superior temporal gyrus, and right superior occipital gyrus. The ReHo value of the left middle temporal gyrus correlated positively with the Hamilton Anxiety Rating Scale scores. Conclusion These results suggest that altered local synchronization of spontaneous brain activity may be related to the pathophysiology of GAD. PMID:28790831

Effect of desipramine and fluoxetine on energy metabolism of cerebral mitochondria.

PubMed

Villa, Roberto Federico; Ferrari, Federica; Gorini, Antonella; Brunello, Nicoletta; Tascedda, Fabio

2016-08-25

Brain bioenergetic abnormalities in mood disorders were detected by neuroimaging in vivo studies in humans. Because of the increasing importance of mitochondrial pathogenetic hypothesis of Depression, in this study the effects of sub-chronic treatment (21days) with desipramine (15mg/kg) and fluoxetine (10mg/kg) were evaluated on brain energy metabolism. On mitochondria in vivo located in neuronal soma (somatic) and on mitochondria of synapses (synaptic), the catalytic activities of regulatory enzymes of mitochondrial energy-yielding metabolic pathways were assayed. Antidepressants in vivo treatment modified the activities of selected enzymes of different mitochondria, leading to metabolic modifications in the energy metabolism of brain cortex: (a) the enhancement of cytochrome oxidase activity on somatic mitochondria; (b) the decrease of malate, succinate dehydrogenase and glutamate-pyruvate transaminase activities of synaptic mitochondria; (c) the selective effect of fluoxetine on enzymes related to glutamate metabolism. These results overcome the conflicting data so far obtained with antidepressants on brain energy metabolism, because the enzymatic analyses were made on mitochondria with diversified neuronal in vivo localization, i.e. on somatic and synaptic. This research is the first investigation on the pharmacodynamics of antidepressants studied at subcellular level, in the perspective of (i) assessing the role of energy metabolism of cerebral mitochondria in animal models of mood disorders, and (ii) highlighting new therapeutical strategies for antidepressants targeting brain bioenergetics. Copyright © 2016 IBRO. Published by Elsevier Ltd. All rights reserved.

Neural signatures of cognitive and emotional biases in depression

PubMed Central

Fossati, Philippe

2008-01-01

Functional brain imaging studies suggest that depression is a system-level disorder affecting discrete but functionally linked cortical and limbic structures, with abnormalities in the anterior cingulate, lateral, ami medial prefrontal cortex, amygdala, ami hippocampus. Within this circuitry, abnormal corticolimbic interactions underlie cognitive deficits ami emotional impairment in depression. Depression involves biases toward processing negative emotional information and abnormal self-focus in response to emotional stimuli. These biases in depression could reflect excessive analytical self-focus in depression, as well as impaired cognitive control of emotional response to negative stimuli. By combining structural and functional investigations, brain imaging studies mav help to generate novel antidepressant treatments that regulate structural and factional plasticity within the neural network regulating mood and affective behavior.

Pregnancy Complications: Umbilical Cord Abnormalities

MedlinePlus

... before and during delivery, which may contribute to cerebral palsy and other forms of brain damage References Cruikshank, ... before and during delivery, which may contribute to cerebral palsy and other forms of brain damage References Cruikshank, ...

Genetics Home Reference: acrocallosal syndrome

MedlinePlus

... callosum occurs when the tissue that connects the left and right halves of the brain (the corpus callosum ) fails to form normally during the early stages of development before birth. Other brain abnormalities, including the growth ...

Insults to the Developing Brain and Impact on Neurodevelopmental Outcome

ERIC Educational Resources Information Center

Adams-Chapman, Ira

2009-01-01

Premature infants have a disproportionately increased risk for brain injury based on several mechanisms including intraventricular hemorrhage, ischemia and the vulnerability of developing neuronal progenitor cells. Injury to the developing brain often results in neurologic abnormalities that can be correlated with a structural lesion; however more…

Frontostriatal connectivity in children during working memory and the effects of prenatal methamphetamine, alcohol, and polydrug exposure.

PubMed

Roussotte, Florence F; Rudie, Jeffrey D; Smith, Lynne; O'Connor, Mary J; Bookheimer, Susan Y; Narr, Katherine L; Sowell, Elizabeth R

2012-01-01

Various abnormalities in frontal and striatal regions have been reported in children with prenatal alcohol and/or methamphetamine exposure. In a recent fMRI study, we observed a correlation between accuracy on a working-memory task and functional activation in the putamen in children with prenatal methamphetamine and polydrug exposure. Because the putamen is part of the corticostriatal motor loop whereas the caudate is involved in the executive loop, we hypothesized that a loss of segregation between distinct corticostriatal networks may occur in these participants. The current study was designed to test this hypothesis using functional connectivity MRI. We examined 50 children ranging in age from 7 to 15, including 19 with prenatal methamphetamine exposure (15 of whom had concomitant prenatal alcohol exposure), 13 with prenatal exposure to alcohol but not methamphetamine, and 18 unexposed controls. We measured the coupling between blood oxygenation level dependent (BOLD) fluctuations during a working-memory task in four striatal seed regions and those in the rest of the brain. We found that the putamen seeds showed increased connectivity with frontal brain regions involved in executive functions while the caudate seeds showed decreased connectivity with some of these regions in both groups of exposed subjects compared to controls. These findings suggest that localized brain abnormalities resulting from prenatal exposure to alcohol and/or methamphetamine lead to a partial rewiring of corticostriatal networks. These results represent important progress in the field, and could have substantial clinical significance in helping devise more targeted treatments and remediation strategies designed to better serve the needs of this population. Copyright © 2012 S. Karger AG, Basel.

Clusters of Low (18)F-Fluorodeoxyglucose Uptake Voxels in Combat Veterans with Traumatic Brain Injury and Post-Traumatic Stress Disorder.

PubMed

Buchsbaum, Monte S; Simmons, Alan N; DeCastro, Alex; Farid, Nikdokht; Matthews, Scott C

2015-11-15

Individuals with mild traumatic brain injury (TBI) show diminished metabolic activity when studied with positron emission tomography (PET) with (18)F-fluorodeoxyglucose (FDG). Since blast injury may not be localized in the same specific anatomical areas in every patient or may be diffuse, significance probability mapping may be vulnerable to false-negative detection of abnormalities. To address this problem, we used an anatomically independent measure to assess PET scans: increased numbers of contiguous voxels that are 2 standard deviations below values found in an uninjured control group. We examined this in three age-matched groups of male patients: 16 veterans with a history of mild TBI, 17 veterans with both mild TBI and post-traumatic stress disorder (PTSD), and 15 veterans without either condition. After FDG administration, subjects performed a modified version of the California Verbal Learning Task. Clusters of low uptake voxels were identified by computing the mean and standard deviation for each voxel in the healthy combat veteran group and then determining the voxel-based z-score for the patient groups. Abnormal clusters were defined as those that contained contiguous voxels with a z-score <-2. Patients with mild TBI alone and patients with TBI+PTSD had larger clusters of low uptake voxels, and cluster size significantly differentiated the mild TBI groups from combat controls. Clusters were more irregular in shape in patients, and patients also had a larger number of low-activity voxels throughout the brain. In mild TBI and TBI+PTSD patients, but not healthy subjects, cluster volume was significantly correlated with verbal learning during FDG uptake.

Dysmorphology and microstructural degradation of the corpus callosum: Interaction of age and alcoholism.

PubMed

Pfefferbaum, Adolf; Adalsteinsson, Elfar; Sullivan, Edith V

2006-07-01

Chronic alcohol abuse is a ubiquitous health and societal problem, with a growing prevalence in the older population. Alcoholism is a source of substantial deterioration in brain tissue and has been consistently observed in vivo and postmortem in white matter. To quantify the potential compounded effect of age and alcoholism, we used conventional structural MRI and diffusion tensor imaging (DTI) to examine the macrostructural and microstructural integrity of the corpus callosum, one of the most prominent white matter structures of the brain, in 131 adults, age 27-75 years. Compared with the 74 controls, the 40 alcoholic men and 17 alcoholic women, who were abstinent from alcohol for an average of 3 months, showed similar patterns and extents of callosal shrinkage, which was greatest in the genu and body and less prominent in the splenium. Microstructural integrity was measured with DTI as fractional anisotropy, an index of intravoxel orientational coherence of white matter fibers, and bulk mean diffusivity, an index of the amount of intravoxel water motility. The macrostructural shrinkage was accompanied by abnormalities in anisotropy and diffusivity of the microstructural environment of these callosal regions, indicative of disruption of structural constituents of local brain white matter. Correlational analyses revealed an age-alcohol interaction, where older alcoholics had smaller genu and splenium and higher diffusivity in these regions than younger alcoholics. Significant correlations between regional MRI and DTI measures and performance on working memory, visuospatial ability, and gait and balance provided evidence for the functional ramifications of the callosal abnormalities in the alcoholics. Thus, despite abstinence from alcohol, the interaction of age and recent alcoholism history exerted a compounded untoward effect on callosal macrostructure and microstructure.

Magnetic resonance imaging of the brain in epileptic adult patients: experience in Ramathibodi Hospital.

PubMed

Solosrungruang, Anusorn; Laothamatas, Jiraporn; Chinwarun, Yotin

2007-04-01

The purpose of the present study was to classify the imaging structural abnormalities of epileptic adult patients referred for magnetic resonance imaging (MR imaging) of the brain at Ramathibodi Hospital and to correlate with the clinical data and EEG. MR imaging of 91 adult epileptic patients (age ranging from 15-85 years old with an average of 36.90 years old) were retrospectively reviewed and classified into eight groups according to etiologies. Then clinical data and EEG correlations were analyzed using the Kappa analysis. All of the MR imaging of the brain were performed at Ramathibodi Hospital from January 2001 to December 2002. Secondary generalized tonic clonic seizure was the most common clinical presenting seizure type. Extra temporal lobe epilepsy was the most common clinical diagnosis. Of the thirty-three patients who underwent EEG before performing MR imaging, 17 had normal EEG From MR imaging, temporal lobe lesion was the main affected location and mesial temporal sclerosis (MTS) was the most common cause of the epilepsy in patients. For age group classification, young adult (15-34 years old) and adult (35-64 years old) age groups, MTS was the most common etiology of epilepsy with cortical dysplasia being the second most common cause for the first group and vascular disease for the latter group. For the older age group (> 64 years old), vascular disease and idiopathic cause were equally common etiologies. MRI, EEG findings, and clinical data were all concordant with statistical significance. MRI is the non-invasive modality of choice for evaluation of the epileptic patients. The result is concordant with the clinical and EEG findings. It can detect and localize the structural abnormality accurately and is useful in the treatment planning.

Resting-state brain networks in patients with Parkinson's disease and impulse control disorders.

PubMed

Tessitore, Alessandro; Santangelo, Gabriella; De Micco, Rosa; Giordano, Alfonso; Raimo, Simona; Amboni, Marianna; Esposito, Fabrizio; Barone, Paolo; Tedeschi, Gioacchino; Vitale, Carmine

2017-09-01

To investigate intrinsic neural networks connectivity changes in Parkinson's disease (PD) patients with and without impulse control disorders (ICD). Fifteen patients with PD with ICD (ICD+), 15 patients with PD without ICD (ICD-) and 24 age and sex-matched healthy controls (HC) were enrolled in the study. To identify patients with and without ICD and/or punding, we used the Minnesota Impulsive Disorders Interview (MIDI) and a clinical interview based on diagnostic criteria for each symptom. All patients underwent a detailed neuropsychological evaluation. Whole brain structural and functional imaging was performed on a 3T GE MR scanner. Statistical analysis of functional data was completed using BrainVoyager QX software. Voxel-based morphometry (VBM) was used to test whether between-group differences in resting-state connectivity were related to structural abnormalities. The presence of ICD symptoms was associated with an increased connectivity within the salience and default-mode networks, as well as with a decreased connectivity within the central executive network (p < .05 corrected). ICD severity was correlated with both salience and default mode networks connectivity changes only in the ICD+ group. VBM analysis did not reveal any statistically significant differences in local grey matter volume between ICD+ and ICD- patients and between all patients and HC (p < .05. FWE). The presence of a disrupted connectivity within the three core neurocognitive networks may be considered as a potential neural correlate of ICD presence in patients with PD. Our findings provide additional insights into the mechanisms underlying ICD in PD, confirming the crucial role of an abnormal prefrontal-limbic-striatal homeostasis in their development. Copyright © 2017 Elsevier Ltd. All rights reserved.

Subtle hemorrhagic brain injury is associated with neurodevelopmental impairment in infants with repaired congenital heart disease.

PubMed

Soul, Janet S; Robertson, Richard L; Wypij, David; Bellinger, David C; Visconti, Karen J; du Plessis, Adré J; Kussman, Barry D; Scoppettuolo, Lisa A; Pigula, Frank; Jonas, Richard A; Newburger, Jane W

2009-08-01

Perioperative stroke and periventricular leukomalacia have been reported to occur commonly in infants with congenital heart disease. We aimed to determine the incidence and type of brain injury in infants undergoing 2-ventricle repair in infancy and to determine risk factors associated with such injury. Forty-eight infants enrolled in a trial comparing 2 different hematocrits during surgical repair of congenital heart disease underwent brain magnetic resonance imaging scans and neurodevelopmental testing at 1 year of age. Eighteen (38%) of our subjects had tiny foci of hemosiderin by susceptibility imaging, without evidence of abnormalities in corresponding regions on conventional magnetic resonance imaging sequences. Subjects with foci of hemosiderin had a significantly lower Psychomotor Developmental Index at 1 year of age (79.6 +/- 16.5, mean +/- standard deviation) compared with subjects without these foci (89.5 +/- 15.3; P = .04). Older age at surgery and diagnostic group were significantly associated with the presence of hemosiderin foci. Only 1 subject had a small stroke (2%), and 2 subjects had periventricular leukomalacia (4%). Foci of hemosiderin without radiologic evidence of ischemic brain injury are an abnormality associated with adverse neurodevelopmental outcome not previously described in magnetic resonance imaging studies of children with surgically repaired congenital heart disease. The association of hemosiderin foci with older age at surgery and cardiac diagnosis, and not with risk factors associated with brain injury, in previous studies suggests that the cause and pathogenesis of this abnormality are different from ischemic brain lesions reported previously.